Guilt is effectively induced by a written auto-biographical essay but not reduced by experimental pain.

Introduction The aim of the present study was (1) to validate the method of guilt-induction by means of a written auto-biographical essay and (2) to test whether experimental pain is apt to alleviate the mental burden of guilt, a concept receiving support from both empirical research and clinical observation. Methods Three independent groups of healthy male participants were recruited. Group allocation was not randomized but within group pain/sham administration was counterbalanced over the two test-days. Groups were tested in the following consecutive order: Group A: guilt induction, heat-pain/sham, N = 59; Group B: guilt induction, cold-pressure-pain/sham, N = 43; Group C: emotionally neutral induction, heat-pain/sham, N = 39. Guilt was induced on both test-days in group A and B before pain/sham administration. Visual analog scale (VAS) guilt ratings immediately after pain/sham stimulation served as the primary outcome. In a control group C the identical heat-pain experiment was performed like in group A but a neutral emotional state was induced. Results A consistently strong overall effect of guilt-induction (heat-pain: p < 0.001, effect size r = 0.71; CPT-pain p < 0.001, r = 0.67) was found when compared to the control-condition (p = 0.25, r = 0.08). As expected, heat- and cold-pressure-stimuli were highly painful in all groups (p < 0.0001, r = 0.89). However, previous research supporting the hypothesis that pain is apt to reduce guilt was not replicated. Conclusion Although guilt-induction was highly effective on both test-days no impact of pain on behavioral guilt-ratings in healthy individuals could be identified. Guilt induction per se did not depend on the order of testing. The result questions previous experimental work on the impact of pain on moral emotions

Sigma factor mimicry involved in regulation of general stress response

Bacteria have evolved regulatory traits to rapidly adapt to changing conditions. Two principal regulatory mechanisms to modulate gene expression consist of regulation via alternative sigma factors and phosphorylation-dependent response regulators. PhyR represents a recently discovered protein family combining parts of both systems: a sigma factor-like domain of the extracytoplasmic function (ECF) subfamily linked to a receiver domain of a response regulator. Here we investigated the mode of action of this key regulator of general stress response in Methylobacterium extorquens. Our results indicate that PhyR does not act as a genuine sigma factor but instead controls gene expression indirectly through protein-protein interactions. This is evident from the analysis of additional proteins involved in PhyR-dependent gene regulation. We demonstrated that the ECF sigma factor-like domain of PhyR interacts with a protein, designated NepR, upon phosphorylation of the PhyR receiver domain. Using transcriptome analysis and phenotypic assays, we showed that NepR is a negative regulator of PhyR response. Furthermore, we provide biochemical and genetic evidence that NepR exerts this inhibitory effect through sequestration of the ECF sigma factor sigma(EcfG1). Our data support an unprecedented model according to which PhyR acts as a mimicry protein triggering a partner-switching mechanism. Such a regulation of general stress response clearly differs from the two known models operating via sigma(S) and sigma(B). Given the absence of these master regulators and the concomitant conservation of PhyR in Alphaproteobacteria, the novel mechanism presented here is most likely central to the control of general stress response in this large subclass of Proteobacteria