Histaminylation of glutamine residues is a novel posttranslational modification implicated in G-protein signaling

Posttranslational modifications (PTM) have been shown to be essential for protein function and signaling. Here we report the identification of a novel modification, protein transfer of histamine, and provide evidence for its function in G protein signaling. Histamine, known as neurotransmitter and mediator of the inflammatory response, was found incorporated into mastocytoma proteins. Histaminylation was dependent on transglutaminase II. Mass spectrometry confirmed histamine modification of the small and heterotrimeric G proteins Cdc42, Galphao1 and Galphaq. The modification was specific for glutamine residues in the catalytic core, and triggered their constitutive activation. TGM2-mediated histaminylation is thus a novel PTM that functions in G protein signaling. Protein alphamonoaminylations, thus including histaminylation, serotonylation, dopaminylation and norepinephrinylation, hence emerge as a novel class of regulatory PTMs

Emotional Cues during Simultaneous Face and Voice Processing: Electrophysiological Insights

Both facial expression and tone of voice represent key signals of emotional communication but their brain processing correlates remain unclear. Accordingly, we constructed a novel implicit emotion recognition task consisting of simultaneously presented human faces and voices with neutral, happy, and angry valence, within the context of recognizing monkey faces and voices task. To investigate the temporal unfolding of the processing of affective information from human face-voice pairings, we recorded event-related potentials (ERPs) to these audiovisual test stimuli in 18 normal healthy subjects; N100, P200, N250, P300 components were observed at electrodes in the frontal-central region, while P100, N170, P270 were observed at electrodes in the parietal-occipital region. Results indicated a significant audiovisual stimulus effect on the amplitudes and latencies of components in frontal-central (P200, P300, and N250) but not the parietal occipital region (P100, N170 and P270). Specifically, P200 and P300 amplitudes were more positive for emotional relative to neutral audiovisual stimuli, irrespective of valence, whereas N250 amplitude was more negative for neutral relative to emotional stimuli. No differentiation was observed between angry and happy conditions. The results suggest that the general effect of emotion on audiovisual processing can emerge as early as 200 msec (P200 peak latency) post stimulus onset, in spite of implicit affective processing task demands, and that such effect is mainly distributed in the frontal-central region

Convergent Evolution of Escape from Hepaciviral Antagonism in Primates

Escape from antagonism by hepatitis C and related viruses has repeatedly evolved in antiviral factor MAVS via convergent evolution, revealing an ancient history of previous viral encounters in primates

Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells during pregnancy

AIMS/HYPOTHESIS: Upregulation of the functional beta cell mass is required to match the physiological demands of mother and fetus during pregnancy. This increase is dependent on placental lactogens (PLs) and prolactin receptors, but the mechanisms underlying these events are only partially understood. We studied the mRNA expression profile of mouse islets during pregnancy to gain a better insight into these changes. METHODS: RNA expression was measured ex vivo via microarrays and quantitative RT-PCR. In vivo observations were extended by in vitro models in which ovine PL was added to cultured mouse islets and MIN6 cells. RESULTS: mRNA encoding both isoforms of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase (TPH), i.e. Tph1 and Tph2, were strongly induced (fold change 25- to 200-fold) during pregnancy. This induction was mimicked by exposing islets or MIN6 cells to ovine PLs for 24 h and was dependent on janus kinase 2 and signal transducer and activator of transcription 5. Parallel to Tph1 mRNA and protein induction, islet serotonin content increased to a peak level that was 200-fold higher than basal. Interestingly, only a subpopulation of the beta cells was serotonin-positive in vitro and in vivo. The stored serotonin pool in pregnant islets and PL-treated MIN6 cells was rapidly released (turnover once every 2 h). CONCLUSIONS/INTERPRETATION: A very strong lactogen-dependent upregulation of serotonin biosynthesis occurs in a subpopulation of mouse islet beta cells during pregnancy. Since the newly formed serotonin is rapidly released, this lactogen-induced beta cell function may serve local or endocrine tasks, the nature of which remains to be identified

The development of cross-cultural recognition of vocal emotion during childhood and adolescence

Humans have an innate set of emotions recognised universally. However, emotion recognition also depends on socio-cultural rules. Although adults recognise vocal emotions universally, they identify emotions more accurately in their native language. We examined developmental trajectories of universal vocal emotion recognition in children. Eighty native English speakers completed a vocal emotion recognition task in their native language (English) and foreign languages (Spanish, Chinese, and Arabic) expressing anger, happiness, sadness, fear, and neutrality. Emotion recognition was compared across 8-to-10, 11-to-13-year-olds, and adults. Measures of behavioural and emotional problems were also taken. Results showed that although emotion recognition was above chance for all languages, native English speaking children were more accurate in recognising vocal emotions in their native language. There was a larger improvement in recognising vocal emotion from the native language during adolescence. Vocal anger recognition did not improve with age for the non-native languages. This is the first study to demonstrate universality of vocal emotion recognition in children whilst supporting an “in-group advantage” for more accurate recognition in the native language. Findings highlight the role of experience in emotion recognition, have implications for child development in modern multicultural societies and address important theoretical questions about the nature of emotions

Inactivation of murine norovirus by chemical biocides on stainless steel

<p>Abstract</p> <p>Background</p> <p>Human norovirus (NoV) causes more than 80% of nonbacterial gastroenteritis in Europe and the United States. NoV transmission via contaminated surfaces may be significant for the spread of viruses. Therefore, measures for prevention and control, such as surface disinfection, are necessary to interrupt the dissemination of human NoV. Murine norovirus (MNV) as a surrogate for human NoV was used to study the efficacy of active ingredients of chemical disinfectants for virus inactivation on inanimate surfaces.</p> <p>Methods</p> <p>The inactivating properties of different chemical biocides were tested in a quantitative carrier test with stainless steel discs without mechanical action. Vacuum-dried MNV was exposed to different concentrations of alcohols, peracetic acid (PAA) or glutaraldehyde (GDA) for 5 minutes exposure time. Detection of residual virus was determined by endpoint-titration on RAW 264.7 cells.</p> <p>Results</p> <p>PAA [1000 ppm], GDA [2500 ppm], ethanol [50% (v/v)] and 1-propanol [30% (v/v)] were able to inactivate MNV under clean conditions (0.03% BSA) on the carriers by ≥ 4 log₁₀within 5 minutes exposure time, whereas 2-propanol showed a reduced effectiveness even at 60% (v/v). Furthermore, there were no significant differences in virus reduction whatever interfering substances were used. When testing with ethanol, 1- and 2-propanol, results under clean conditions were nearly the same as in the presence of dirty conditions (0.3% BSA plus 0.3% erythrocytes).</p> <p>Conclusion</p> <p>Products based upon PAA, GDA, ethanol and 1-propanol should be used for NoV inactivation on inanimate surfaces. Our data provide valuable information for the development of strategies to control NoV transmission via surfaces.</p

Intracellular Serotonin Modulates Insulin Secretion from Pancreatic β-Cells by Protein Serotonylation

Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion

Effect of Peripheral 5-HT on Glucose and Lipid Metabolism in Wether Sheep

In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR) antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species