Atmung, Aufmerksamkeit und Ablenkung als Funktion emotionaler Stimuli: Ablenkung, Atmung, Aufmerksamkeit, Emotion, Erregung, Valenz

Mittels Bilder, Musikstücken und Geräuschen induzierten wir Emotionen und gingen einerseits der Frage nach, wie emotionale Bewertung und physiologische Vorgänge, insbesondere die Atmung, miteinander verknüpft sind. Andererseits untersuchten wir mit Geruchsexpositionen während einer Mehrfachverrichtung, welche Rolle die Geruchs-Valenz bei der Arbeitsablenkung spielt. Unsere Versuche zeigten, dass die Atmungsantworten auf induzierte Emotionen in einem gewissen Rahmen dem Dimensionsmodell von Valenz und Arousal folgten, insbesondere bildeten sie die induzierte Erregung konsistent ab. Auch das Aufmerksamkeits-Engagement hing von der emotionalen Bedeutung des Stimulus ab, da nur die negativ attribuierten Gerüche eine Leistungsminderung in der Mehrfachverrichtung auslösten. [Autoren]

Tissue-specific opposing functions of the inflammasome adaptor ASC in the regulation of epithelial skin carcinogenesis.

A chronic inflammatory microenvironment favors tumor progression through molecular mechanisms that are still incompletely defined. In inflammation-induced skin cancers, IL-1 receptor- or caspase-1-deficient mice, or mice specifically deficient for the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) in myeloid cells, had reduced tumor incidence, pointing to a role for IL-1 signaling and inflammasome activation in tumor development. However, mice fully deficient for ASC were not protected, and mice specifically deficient for ASC in keratinocytes developed more tumors than controls, suggesting that, in contrast to its proinflammatory role in myeloid cells, ASC acts as a tumor-suppressor in keratinocytes. Accordingly, ASC protein expression was lost in human cutaneous squamous cell carcinoma, but not in psoriatic skin lesions. Stimulation of primary mouse keratinocytes or the human keratinocyte cell line HaCaT with UVB induced an ASC-dependent phosphorylation of p53 and expression of p53 target genes. In HaCaT cells, ASC interacted with p53 at the endogenous level upon UVB irradiation. Thus, ASC in different tissues may influence tumor growth in opposite directions: it has a proinflammatory role in infiltrating cells that favors tumor development, but it also limits keratinocyte proliferation in response to noxious stimuli, possibly through p53 activation, which helps suppressing tumors.

Pneumolysin Activates the NLRP3 Inflammasome and Promotes Proinflammatory Cytokines Independently of TLR4.

Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1β, IL-1α and TNF-α by DC and enhanced cytokines including IL-17A and IFN-γ by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-γ are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-γ and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1β plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1β secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system.

Test-retest repeatability of the pupil light response to blue and red light stimuli in normal human eyes using a novel pupillometer.

In this study, we evaluated the repeatability of pupil responses to colored light stimuli in healthy subjects using a prototype chromatic pupillometer. One eye of 10 healthy subjects was tested twice in the same day using monochromatic light exposure at two selected wavelengths (660 and 470 nm, intensity 300 cd/m(2)) presented continuously for 20 s. Pupil responses were recorded in real-time before, during, and after light exposure. Maximal contraction amplitude and sustained contraction amplitude were calculated. In addition, we quantified the summed pupil response during continuous light stimulation as the total area between a reference line representing baseline pupil size and the line representing actual pupil size over 20 s (area under the curve). There was no significant difference in the repeated measure compared to the first test for any of the pupil response parameters. In conclusion, we have developed a novel prototype of color pupillometer which demonstrates good repeatability in evoking and recording the pupillary response to a bright blue and red light stimulus.

Stroking or Buzzing? A Comparison of Somatosensory Touch Stimuli Using 7 Tesla fMRI.

Studying body representations in the brain helps us to understand how we humans relate to our own bodies. The in vivo mapping of the somatosensory cortex, where these representations are found, is greatly facilitated by the high spatial resolution and high sensitivity to brain activation available at ultra-high field. In this study, the use of different stimulus types for somatotopic mapping of the digits at ultra-high field, specifically manual stroking and mechanical stimulation, was compared in terms of sensitivity and specificity of the brain responses. Larger positive responses in digit regions of interest were found for manual stroking than for mechanical stimulation, both in terms of average and maximum t-value and in terms of number of voxels with significant responses to the tactile stimulation. Responses to manual stroking were higher throughout the entire post-central sulcus, but the difference was especially large on its posterior wall, i.e. in Brodmann area 2. During mechanical stimulation, cross-digit responses were more negative than during manual stroking, possibly caused by a faster habituation to the stimulus. These differences indicate that manual stroking is a highly suitable stimulus for fast somatotopic mapping procedures, especially if Brodmann area 2 is of interest.

Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP) as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA). The formulations included (1) trimethyl chitosan (TMC) nanoparticles, (2) a squalene-in-water nanoemulsion, and (3) a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9). In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2) was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used.

Timing of visual stimuli in V1 and V5/MT: fMRI and TMS

Time perception is used in our day-to-day activities. While we understand quite well how our brain processes vision, touch or taste, brain mechanisms subserving time perception remain largely understudied. In this study, we extended an experiment of previous master thesis run by Tatiana Kenel-Pierre. We focused on time perception in the range of milliseconds. Previous studies have demonstrated the involvement of visual areas V1 and V5/MT in the encoding of temporal information of visual stimuli. Based on these previous findings the aim of the present study was to understand if temporal information was encoded in V1 and extrastriate area V5/MT in different spatial frames i.e., head- centered versus eye-centered. To this purpose we asked eleven healthy volunteers to perform a temporal discrimination task of visual stimuli. Stimuli were presented at 4 different spatial positions (i.e., different combinations of retinotopic and spatiotopic position). While participants were engaged in this task we interfered with the activity of the right dorsal V1 and the right V5/MT with transcranial magnetic stimulation (TMS). Our preliminary results showed that TMS over both V1 and V5/MT impaired temporal discrimination of visual stimuli presented at specific spatial coordinates. But whereas TMS over V1 impaired temporal discrimination of stimuli presented in the lower left quadrant, TMS over V5/MT affected temporal discrimination of stimuli presented at the top left quadrant. Although it is always difficult to draw conclusions from preliminary results, we could tentatively say that our data seem to suggest that both V1 and V5/MT encode visual temporal information in specific spatial frames.

Stimuli investigandi Gog in Magog

Invocatio: I.N.J.

Response threshold to aversive stimuli in stimulated early protein-malnourished rats

Two animal models of pain were used to study the effects of short-term protein malnutrition and environmental stimulation on the response threshold to aversive stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age while the mothers of the other half (controls) were well nourished, receiving 16% protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the animals in the malnourished and control groups were maintained under stimulating conditions, including a 3-min daily handling from 0 to 70 days and an enriched living cage after weaning. The other half was reared in a standard living cage. At 70 days, independent groups of rats were exposed to the shock threshold or to the tail-flick test. The results showed lower body and brain weights in malnourished rats when compared with controls at weaning and testing. In the shock threshold test the malnourished animals were more sensitive to electric shock and environmental stimulation increased the shock threshold. No differences due to diet or environmental stimulation were found in the tail-flick procedure. These results demonstrate that protein malnutrition imposed only during the lactation period is efficient in inducing hyperreactivity to electric shock and that environmental stimulation attenuates the differences in shock threshold produced by protein malnutrition

Contrast sensitivity to angular frequency stimuli is higher than that for sinewave gratings in the respective middle range

This study compares contrast thresholds for sinewave gratings, or spatial frequencies (1/CSF) with contrast thresholds for angular frequencies (1/aCSF) and for radial frequencies, or J0 targets (1/rCSF). Observers had to differentiate between one of these frequency stimuli and a stimulus at mean luminance within a forced-choice procedure. All measurements were made with the same equipment, methods and subjects. Our results show higher sensitivity to, or lower thresholds for, angular frequencies when compared to either sinewave gratings or J0 targets. Contrast values in arbitrary units, in the lower threshold range for angular frequencies, were about half those required to differentiate sinewave gratings from mean luminance in its most sensitive range

Inhibitory effects in the detection of 1 cpd jo targets superimposed to angular frequency stimuli or sinewave gratings

Independence among channels processing different aspects of spatial information, including orthogonal stimuli, has been generally assumed in the literature. We tested independence between the processing of jo targets and the processing of either vertical sinusoidal gratings or angular frequency stimuli with suprathreshold summation. We found the detection of a jo target at 1 cpd to be affected in an inhibitory fashion by either background angular frequencies in the range of 3-96 cycles or sinewave gratings in the range of 0.8-3.0 cpd. These results demonstrate interactions both among orthogonal stimuli and among channels processing vertical sinewave gratings and jo target stimuli. Our discussion focuses on the hypothesis of frequency decomposition in polar coordinates

Paradoxical increase of exploratory behavior in the elevated plus-maze by rats exposed to two kinds of aversive stimuli

Albino rats were submitted to a 24-h period of social isolation (individual housing) combined with 0, 1, 2 or 3 twenty-four-hour periods of exposure to different vivaria (novelty) and tested in the elevated plus-maze. Results, reported as mean ± SEM for N = 12, show that the time (in seconds) spent in the open arms by rats exposed to novelty for 0, 1, 2 and 3 days was 28.3 ± 4.4, 31.6 ± 3.2, 29.1 ± 3.5 and 25.0 ± 3.3, respectively, when grouped in the same vivarium; 29.6 ± 2.7, 7.6 ± 2.1, 9.6 ± 4.4 and 28.5 ± 3.7 when grouped in different vivaria; 2.9 ± 1.1, 1.8 ± 1.0, 2.7 ± 1.1 and 0 ± 0 when isolated in the same vivarium, and 2.6 ± 1.1, 31.5 ± 8.2, 24.8 ± 4.2 and 0 ± 0 when isolated in different vivaria. The number of entries into the open and closed arms followed a similar trend. This indicates that, separately, both exposure to novelty and isolation are aversive manipulations. Paradoxically, when novelty was combined with a concomitant 24-h period of social isolation prior to testing, the decrease in exploratory behavior caused by either of the two aversive manipulations alone was reverted. These results are indicative that less intense anxiety triggers mechanisms mediating less energetic behavior such as freezing, while higher levels trigger mechanisms mediating more vigorous action, such as flight/fight behavior, since the combination of two aversive situations resulted in more exploratory behavior than with either alone. They are also suggestive of habituation to the effects of novelty, since exposure to it for 3 days produced exploratory behavior similar to that of controls