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Victims of urban violence are at risk of developing Posttraumatic Stress Disorder (PTSD), one of the most debilitating consequences of violence. Considering that PTSD may be associated with inefficient selection of defensive responses, it is important to understand the relation between motor processing and PTSD. The present study aims to investigate the extent to which the severity of posttraumatic stress symptoms (PTSS) is related to motor preparation against visual threat cues in victims of urban violence. Participants performed a choice reaction time task while ignoring a picture that could be threating or neutral. The EEG indices extracted were the motor-related amplitude asymmetry (MRAA) in the alpha frequency range, and the lateralized readiness potential (LRP). We observed a linear relation between longer LRP latency and a slower reaction time, selectively during threat processing (compared to neutral) in low PTSS, but not in high PTSS participants. Alpha MRAA suppression and the PTSS were also linearly related the smaller the alpha MRAA suppression in the threat condition relative to neutral, the greater the PTSS. These results provide evidence that threatening cues affect motor processing that is modulated by the severity of PTSS in victims of urban violence.Observing others performing motor acts like grasping has been shown to elicit neural responses in the observer`s parieto-frontal motor network, which typically becomes active when the observer would perform these actions him/herself. While some human studies suggested strongest motor resonance during observation of first person or egocentric perspectives compared to third person or allocentric perspectives, other research either report the opposite or did not find any viewpoint-related preferences in parieto-premotor cortices. Furthermore, it has been suggested that these motor resonance effects are lateralized in the parietal cortex depending on the viewpoint and identity of the observed effector (left vs right hand). Other studies, however, do not find such straightforward hand identity dependent motor resonance effects. In addition to these conflicting findings in human studies, to date, little is known about the modulatory role of viewing perspective and effector identity (left or right hand) on motor resonance effects in monkey parieto-premotor cortices. Here, we investigated the extent to which different viewpoints of observed conspecific hand actions yield motor resonance in rhesus monkeys using fMRI. Observing first person, lateral and third person viewpoints of conspecific hand actions yielded significant activations throughout the so-called action observation network, including STS, parietal and frontal cortices. Although region-of-interest analysis of parietal and premotor motor/mirror neuron regions AIP, PFG and F5, showed robust responses in these regions during action observation in general, a clear preference for egocentric or allocentric perspectives was not evident. Moreover, except for lateralized effects due to visual field biases, motor resonance in the monkey brain during grasping observation did not reflect hand identity dependent coding.The shared representations account of empathy suggests that sharing other people's emotions relies on neural processes similar to those engaged when directly experiencing such emotions. Recent research corroborated this by showing that placebo analgesia induced for first-hand pain resulted in reduced pain empathy and decreased activation in shared neural networks. However, those studies did not report any placebo-related variation of somatosensory engagement during pain empathy. The experimental paradigms used in these studies did not direct attention towards a specific body part in pain, which may explain the absence of effects for somatosensation. The main objective of this preregistered study was to implement a paradigm overcoming this limitation, and to investigate whether placebo analgesia may also modulate the sensory-discriminative component of empathy for pain. We induced a localized, first-hand placebo analgesia effect in the right hand of 45 participants by means of a placebo gel and conditioning techniques, and compared this to the left hand as a control condition. Participants underwent a pain task in the MRI scanner, receiving painful or non-painful electrical stimulation on their left or right hand, or witnessing another person receiving such stimulation. In contrast to a robust localized placebo analgesia effect for self-experienced pain, the empathy condition showed no differences between the two hands, neither for behavioral nor neural responses. We thus report no evidence for somatosensory sharing in empathy, while replicating previous studies showing overlapping brain activity in the affective-motivational component for first-hand and empathy for pain. Hence, in a more rigorous test aiming to overcome limitations of previous work, we again find no causal evidence for the engagement of somatosensory sharing in empathy. Our study refines the understanding of the neural underpinnings of empathy for pain, and the use of placebo analgesia in investigating such models.Brusatol, a quassinoid natural product, is effective against multiple diseases including hematologic malignancies, as we reported recently by targeting the PI3Kγ isoform, but toxicity limits its further development. Herein, we report the synthesis of a series of conjugates of brusatol with amino acids and short peptides at its enolic hydroxyl at C-3. A number of conjugates with smaller amino acids and peptides demonstrated activities comparable to brusatol. Through in vitro and in vivo evaluations, we identified UPB-26, a conjugate of brusatol with a L- β-homoalanine, which exhibits good chemical stability at physiological pH's (SGF and SIF), moderate rate of conversion to brusatol in both human and rat plasmas, improved mouse liver microsomal stability, and most encouragingly, enhanced safety compared to brusatol in mice upon IP administration.Myelin is a lipid multilayer involved in the rate of nerve transmission, and its loss is a pathological feature of multiple sclerosis in brains. Since in vivo imaging of myelin may be useful for drug development, early diagnosis, and monitoring the disease stage, we designed, synthesized, and evaluated eight novel radioiodinated 3-phenylcoumarin derivatives as imaging probes targeting myelin. In the biodistribution study using normal mice, all compounds displayed sufficient brain uptake, ranging from 2.5 to 5.0% ID/g, at 2 min postinjection. On ex vivo autoradiography, [125I]18 and [125I]21, which have a dimethylamino group, showed high binding affinity for myelin in the normal mouse brain. In addition, the radioactivity accumulation of [125I]21 in the white matter of the spinal cord in the experimental autoimmune encephalomyelitis mice was lower than that in naive mice. https://www.selleckchem.com/products/Cytarabine(Cytosar-U).html These results suggest that [123I]21 shows potential as a single photon emission computed tomography probe targeting myelin.
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