Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex

The ribbon complex of retinal photoreceptor synapses represents a specialization of the cytomatrix at the active zone (CAZ) present at conventional synapses. In mice deficient for the CAZ protein Bassoon, ribbons are not anchored to the presynaptic membrane but float freely in the cytoplasm. Exploiting this phenotype, we dissected the molecular structure of the photoreceptor ribbon complex. Identifiable CAZ proteins segregate into two compartments at the ribbon: a ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and the motor protein KIF3A, and an active zone compartment including RIM2, Munc13-1, a Ca2+ channel α1 subunit, and ERC2/CAST1. A direct interaction between the ribbon-specific protein RIBEYE and Bassoon seems to link the two compartments and is responsible for the physical integrity of the photoreceptor ribbon complex. Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses, suggesting a novel role for the CtBP/BARS family in the molecular assembly and function of central nervous system synapses

Active zone proteins are dynamically associated with synaptic ribbons in rat pinealocytes

Synaptic ribbons (SRs) are prominent organelles that are abundant in the ribbon synapses of sensory neurons where they represent a specialization of the cytomatrix at the active zone (CAZ). SRs occur not only in neurons, but also in neuroendocrine pinealocytes where their function is still obscure. In this study, we report that pinealocyte SRs are associated with CAZ proteins such as Bassoon, Piccolo, CtBP1, Munc13–1, and the motorprotein KIF3A and, therefore, consist of a protein complex that resembles the ribbon complex of retinal and other sensory ribbon synapses. The pinealocyte ribbon complex is biochemically dynamic. Its protein composition changes in favor of Bassoon, Piccolo, and Munc13–1 at night and in favor of KIF3A during the day, whereas CtBP1 is equally present during the night and day. The diurnal dynamics of the ribbon complex persist under constant darkness and decrease after stimulus deprivation of the pineal gland by constant light. Our findings indicate that neuroendocrine pinealocytes possess a protein complex that resembles the CAZ of ribbon synapses in sensory organs and whose dynamics are under circadian regulation

Emerging issues and current trends in assistive technology use 2007-1010: practising, assisting and enabling learning for all

Following an earlier review in 2007, a further review of the academic literature relating to the uses of assistive technology (AT) by children and young people was completed, covering the period 2007-2011. As in the earlier review, a tripartite taxonomy: technology uses to train or practise, technology uses to assist learning and technology uses to enable learning, was used in order to structure the findings. The key markers for research in this field and during these three years were user involvement, AT on mobile mainstream devices, the visibility of AT, technology for interaction and collaboration, new and developing interfaces and inclusive design principles. The paper concludes by locating these developments within the broader framework of the Digital Divide

Telemedical system for monitoring of blood pressure

It is increasingly clear that the traditional way of measuring blood pressure in the clinic or office frequently produces numbers that grossly overestimate a patient’s true blood pressure level. This effect is often caused by so called „white coat“ syndrome. Nowadays, for this reason it becomes more popular so called home monitoring of blood pressure, that attenuates this effect. In the paper, there is described specially telemedicine system for monitoring of blood pressure. The system consists of blood monitor equipment which automatically reports results of up-to-date patient’s measurements to the doctor’s monitoring and decision support (MDS) system using wireless communication. The MDS system can make an evaluation for the doctor who can immediately intervene if necessary. Introduction of such a system in practice can bring considerable improvement in the treatment of hypertension

Antidepressant ketamine and its metabolite hydroxynorketamine converge on the regulation of neurotransmitter release

Major depressive disorder (MDD) is a devitalizing psychiatric condition with a lifetime prevalence of 17%. Alterations in glutamatergic transmission and plasticity have been closely associated with MDD. Ketamine is an activity-dependent blocker of NMDA receptors (NMDAR) which, at low subanesthetic doses show rapid and sustained antidepressant effect in treatment resistant patients. Changes in neuronal plasticity and synaptic transmission have been associated with antidepressant effects of ketamine. However, psychotomimetic effects and abuse potential of ketamine cannot be ignored and thus, its off-label use remains limited. A fairly recent study suggested that not ketamine but its metabolite hydroxynorketamine (HNK), which does not act via NMDAR, mediates the rapid antidepressant action. The molecular mechanisms of ketamine and HNK induced antidepressant effect remain enigmatic. In this study, we set up to monitor the effects of ketamine and HNK in cultured cortical neurons using live-cell imaging and electrophysiology, to investigate the convergent and divergent effects of these drugs on neurotransmission, signaling and gene expression, at the level of individual cells and synapses. Our results indicate that low doses of ketamine and HNK show convergent effect on neurotransmitter release and thus modulate neurotransmission rapidly and persistently. Hereon, we provide a mechanistic understanding of cellular signaling mediating the antidepressant effect of ketamine and its metabolite HNK