Degeneration and regeneration of peripheral nerves: role of thrombin and its receptor PAR-1

The peripheral nervous system has a striking regeneration potential and after damage extensive changes in the differentiation state both of the injured neurons and of the Schwann cells are observed. Schwann cells, in particular, undergo a large scale change in gene expression becoming able to support axonal regeneration. Nerve injury is generally associated to inflammation and activation of the coagulation cascade. Thrombin acts as a polyfunctional signalling molecule exerting its physiological function through soluble target proteins and G-protein-coupled receptors, the protease-activated receptors (PARs) [1]. Recently, we have demonstrated that the activation of the main thrombin receptor, PAR-1, in Schwann cells favours their regenerative potential determining the release of factors which promote axonal regrowth [2]. The pro-regenerative potential of thrombin seems to be exerted in a narrow range of concentrations (pM-nM range). In fact, our preliminary data indicate that high levels of thrombin in the micromolar range slow down Schwann cell proliferation and induce cell death. On the contrary, PAR-1 activating peptides mimic the pro-survival but not the pro-apoptotic effects of thrombin. Controlling thrombin concentration may preserve neuronal health during nerve injury and represent a novel target for pharmacologic therapies

The Witness-Aimed First Account (WAFA): a new technique for interviewing autistic witnesses and victims

Autistic people experience social communication difficulties alongside specific memory difficulties that can impact their ability to recall episodic events. Police interviewing techniques do not take account of these differences, and so are often ineffective. Here we introduce a novel Witness-Aimed First Account (WAFA) interview technique, designed to better support autistic witnesses by diminishing socio-cognitive and executive demands through encouraging participants to generate and direct their own discrete, parameter-bound event topics, before freely recalling information within each parameter-bound topic. Since witnessed events are rarely cohesive stories with a logical chain of events, we also explored witnesses’ recall when the narrative structure of the to-be-remembered event was lost. Thirty-three autistic and 30 typically developing (TD) participants were interviewed about their memory for two videos depicting criminal events. Clip segments of one video were ‘scrambled’, disrupting the event’s narrative structure; the other video was watched intact. Although both autistic and TD witnesses recalled fewer details with less accuracy from the scrambled video, WAFA interviews resulted in more detailed and accurate recall from autistic and TD witnesses, for both scrambled and unscrambled videos. The WAFA technique may be a useful tool to improve autistic and TD witnesses’ accounts within a legally appropriate, non-leading framework

Memory for Emotionally Arousing Events Over Time in Autism Spectrum Disorder

Emotionally arousing events are typically better remembered and more resistant to forgetting than neutral events. Findings from word list paradigms suggest that this may not hold for individuals with Autism Spectrum Disorder (ASD), who also tend to be less accurate as eyewitnesses under some circumstances. To test whether attenuated effects of arousal on memory may be responsible for poorer eyewitness testimonies in ASD, we asked adults with and without the disorder to view either arousing or neutral versions of a narrated slide sequence (Experiment 1) or video clip (Experiment 2) before assessing their memory for the material. Both groups exhibited increases in psychophysiological arousal during the arousing compared with the neutral version of the narratives, and both groups also demonstrated a memory advantage for the arousing events. Contrary to predictions, these observations indicate that stimulus induced arousal modulates memory for naturalistic events relatively typically in ASD

Memory for Emotionally Arousing Events Over Time in Autism Spectrum Disorder

Emotionally arousing events are typically better remembered and more resistant to forgetting than neutral events. Findings from word list paradigms suggest that this may not hold for individuals with Autism Spectrum Disorder (ASD), who also tend to be less accurate as eyewitnesses under some circumstances. To test whether attenuated effects of arousal on memory may be responsible for poorer eyewitness testimonies in ASD, we asked adults with and without the disorder to view either arousing or neutral versions of a narrated slide sequence (Experiment 1) or video clip (Experiment 2) before assessing their memory for the material. Both groups exhibited increases in psychophysiological arousal during the arousing compared with the neutral version of the narratives, and both groups also demonstrated a memory advantage for the arousing events. Contrary to predictions, these observations indicate that stimulus induced arousal modulates memory for naturalistic events relatively typically in ASD

Mechanism-based Inactivation of Dopa Decarboxylase by Serotonin

Abstract Pig kidney dopa decarboxylase (DDC) expressed in Escherichia coli is a homodimeric enzyme containing one catalytically active pyridoxal 5′-phosphate active site per subunit. In addition to catalyzing the decarboxylation of L-aromatic amino acids, DDC also reacts with 5-hydroxytryptamine (5-HT), converting it to 5-hydroxyindolacetaldehyde and ammonia. These products have been identified by means of the enzymes alcohol dehydrogenase and glutamate dehydrogenase, together with high performance liquid chromatographic and mass spectroscopic analysis. The Kcat and Km values of this reaction were determined to be 0.48 min−1 and 0.47 mM, respectively. The NaBH4-reduced enzyme does not catalyze this reaction. Concurrent with this reaction, 5-HT inactivates DDC in both a time- and concentration-dependent manner and exhibits saturation of the rate of inactivation at high concentrations, with Ki and Kinact values of 0.40 mM and 0.023 min−1, respectively. Protection from inactivation by 5-HT was observed in the presence of the active site-directed inhibitor 3,4-dihydroxy-D-phenylalanine. Inactivation with [2-14C]5-HT results in the incorporation of 1 mol of label/enzyme subunit. Taken together, these findings indicate that 5-HT is both a substrate and a mechanism-based inactivator with a partition ratio for product formation versus inactivation of 21. The absorbance, CD, and fluorometric features of 5-HT-inactivated DDC have also been characterized. A speculative mechanism for the reaction and inactivation consistent with the experimental findings is presented

The primary structure of mitochondrial aspartate aminotrasferase from human heart

The complete amino acid sequence of the mitochondrial asparate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) from human heart has been determined based mainly on analysis of peptides obtained by digestion with trypsin and by chemical cleavage with cyanogen bromide. Comparison of the sequence with those of the isotopic isoenzymes from pig, rat and chicken showed 27, 29 and 55 differences, respectively, out of a total of 401 amino acid residues. Evidence for structural microheterogeneity at position 317 has also been obtained

Mock juror perceptions of child witnesses on the autism spectrum: the impact of providing diagnostic labels and information about autism

Research suggests that autistic children can provide accurate and forensically useful eyewitness evidence. However, members of a jury also rely on non-verbal behaviours when judging the credibility of a witness, and this could determine the verdict of a case. We presented mock jurors with videos (from an experimental study) of one of two child witnesses on the autism spectrum being interviewed about a mock minor crime. Results demonstrated that providing jurors with generic information about autism and/or informing them of the child’s diagnostic label differentially affected credibility ratings, but not for both children. Implications for how to present information about child witnesses with autism to a jury – highlighting the need for approaches tailored to individual children – are discussed