Acute tryptophan depletion attenuates conscious appraisal of social emotional signals in healthy female volunteers

Rationale: Acute tryptophan depletion (ATD) decreases levels of central serotonin. ATD thus enables the cognitive effects of serotonin to be studied, with implications for the understanding of psychiatric conditions, including depression. Objective: To determine the role of serotonin in conscious (explicit) and unconscious/incidental processing of emotional information. Materials and methods: A randomized, double-blind, cross-over design was used with 15 healthy female participants. Subjective mood was recorded at baseline and after 4 h, when participants performed an explicit emotional face processing task, and a task eliciting unconscious processing of emotionally aversive and neutral images presented subliminally using backward masking. Results: ATD was associated with a robust reduction in plasma tryptophan at 4 h but had no effect on mood or autonomic physiology. ATD was associated with significantly lower attractiveness ratings for happy faces and attenuation of intensity/arousal ratings of angry faces. ATD also reduced overall reaction times on the unconscious perception task, but there was no interaction with emotional content of masked stimuli. ATD did not affect breakthrough perception (accuracy in identification) of masked images. Conclusions: ATD attenuates the attractiveness of positive faces and the negative intensity of threatening faces, suggesting that serotonin contributes specifically to the appraisal of the social salience of both positive and negative salient social emotional cues. We found no evidence that serotonin affects unconscious processing of negative emotional stimuli. These novel findings implicate serotonin in conscious aspects of active social and behavioural engagement and extend knowledge regarding the effects of ATD on emotional perception

Effects of Selective Deafferentation on the Discharge Characteristics of Medial Rectus Motoneurons

Medial rectus motoneurons receive two main pontine inputs: abducens internuclear neurons, whose axons course through the medial longitudinal fasciculus (MLF), and neurons in the lateral vestibular nucleus, whose axons project through the ascending tract of Deiters (ATD). Abducens internuclear neurons are responsible for conjugate gaze in the horizontal plane, whereas ATD neurons provide medial rectus motoneurons with a vestibular input comprising mainly head velocity. To reveal the relative contribution of each input to the oculomotor physiology, single-unit recordings from medial rectus motoneurons were obtained in the control situation and after selective deafferentation from cats with unilateral transection of either the MLF or the ATD. Both MLF and ATD transection produced similar short-term alterations in medial rectus motoneuron firing pattern, which were more drastic in MLF of animals. However, long-term recordings revealed important differences between the two types of lesion. Thus, while the effects of the MLF section were permanent, 2 months after ATD lesioning all motoneuronal firing parameters were similar to the control. These findings indicated a more relevant role of the MLF pathway in driving motoneuronal firing and evidenced compensatory mechanisms following the ATD lesion. Confocal immunocytochemistry revealed that MLF transection produced also a higher loss of synaptic boutons, mainly at the dendritic level. Moreover, 2 months after ATD transection, we observed an increase in synaptic coverage around motoneuron cell bodies compared with short-term data, which is indicative of a synaptogenic compensatory mechanism of the abducens internuclear pathway that could lead to the observed firing and morphological recovery. SIGNIFICANCE STATEMENT Eye movements rely on multiple neuronal circuits for appropriate performance. The abducens internuclear pathway through the medial longitudinal fascicle (MLF) and the vestibular neurons through the ascending tract of Deiters (ATD) are a dual system that supports the firing of medial rectus motoneurons. We report the effect of sectioning the MLF or the ATD pathway on the firing of medial rectus motoneurons, as well as the plastic mechanisms by which one input compensates for the lack of the other. This work shows that while the effects of MLF transection are permanent, the ATD section produces transitory effects. A mechanism based on axonal sprouting and occupancy of the vacant synaptic space due to deafferentation is the base for the mechanism of compensation on the medial rectus motoneuron

Awareness, requirements and barriers to use of Assistive Technology designed to enable independence of people suffering from Dementia (ATD)

This article is available through the Brunel Open Access Publishing Fund. Copyright @ 2012 IOS PressThis study investigated the awareness and use of assistive technology for people with dementia. The aim of the study was to explore barriers to the uptake of, and the unmet needs for, assistive technology for dementia (ATD) The work was carried out with family carers of people with dementia because carers are often the purchasers, end users and main beneficiaries of this type of technology. Focus groups were used to explore carers’ views on ATD use, and the problems that might be addressed by ATD, in order to develop a questionnaire for dementia carers. The questionnaire was administered at Alzheimer’s Society carer support groups in South Bucks and in Hillingdon Borough (UK). None of the 16 focus group participants or the 42 respondents to the questionnaire had any personal experience of ATD. The dementia carers reported a number of concerns, problems and unmet needs that could be addressed by existing, commercially available ATD products. Some needs for new technology development were identified in the study, but the lack of awareness of ATD appears to be the most important barrier to technology adoption

Large Space Telescope (LST) Pointing Control System (PCS) analytical Advanced Technical Development (ATD) program

The large space telescope (LST) pointing control system (PCS) advanced technical development (ATD) program is described. The approach used is to describe the overall PCS development effort, showing how the analytical ATD program elements fit into it. Then the analytical ATD program elements are summarized

Deterministic approach to microscopic three-phase traffic theory

Two different deterministic microscopic traffic flow models, which are in the context of the Kerner's there-phase traffic theory, are introduced. In an acceleration time delay model (ATD-model), different time delays in driver acceleration associated with driver behaviour in various local driving situations are explicitly incorporated into the model. Vehicle acceleration depends on local traffic situation, i.e., whether a driver is within the free flow, or synchronized flow, or else wide moving jam traffic phase. In a speed adaptation model (SA-model), vehicle speed adaptation occurs in synchronized flow depending on driving conditions. It is found that the ATD- and SA-models show spatiotemporal congested traffic patterns that are adequate with empirical results. In the ATD- and SA-models, the onset of congestion in free flow at a freeway bottleneck is associated with a first-order phase transition from free flow to synchronized flow; moving jams emerge spontaneously in synchronized flow only. Differences between the ATD- and SA-models are studied. A comparison of the ATD- and SA-models with stochastic models in the context of three phase traffic theory is made. A critical discussion of earlier traffic flow theories and models based on the fundamental diagram approach is presented.Comment: 40 pages, 14 figure

An analog of glibenclamide selectively enhances autophagic degradation of misfolded α1-antitrypsin Z

The classical form of α1-antitrypsin deficiency (ATD) is characterized by intracellular accumulation of the misfolded variant α1-antitrypsin Z (ATZ) and severe liver disease in some of the affected individuals. In this study, we investigated the possibility of discovering novel therapeutic agents that would reduce ATZ accumulation by interrogating a C. elegans model of ATD with high-content genome-wide RNAi screening and computational systems pharmacology strategies. The RNAi screening was utilized to identify genes that modify the intracellular accumulation of ATZ and a novel computational pipeline was developed to make high confidence predictions on repurposable drugs. This approach identified glibenclamide (GLB), a sulfonylurea drug that has been used broadly in clinical medicine as an oral hypoglycemic agent. Here we show that GLB promotes autophagic degradation of misfolded ATZ in mammalian cell line models of ATD. Furthermore, an analog of GLB reduces hepatic ATZ accumulation and hepatic fibrosis in a mouse model in vivo without affecting blood glucose or insulin levels. These results provide support for a drug discovery strategy using simple organisms as human disease models combined with genetic and computational screening methods. They also show that GLB and/or at least one of its analogs can be immediately tested to arrest the progression of human ATD liver disease.</div