Kinematics fingerprints of leader and follower role-taking during cooperative joint actions

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Real-time optical manipulation of cardiac conduction in intact hearts

Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

Enhancement of Magneto-Optic Effects via Large Atomic Coherence

We utilize the generation of large atomic coherence to enhance the resonant nonlinear magneto-optic effect by several orders of magnitude, thereby eliminating power broadening and improving the fundamental signal-to-noise ratio. A proof-of-principle experiment is carried out in a dense vapor of Rb atoms. Detailed numerical calculations are in good agreement with the experimental results. Applications such as optical magnetometry or the search for violations of parity and time reversal symmetry are feasible

Fast optical investigation of cardiac electrophysiology by parallel detection in multiwell plates

Current techniques for fast characterization of cardiac electrophysiology employ optical technologies to control and monitor action potential features of single cells or cellular monolayers placed in multiwell plates. High-speed investigation capacities are commonly achieved by serially analyzing well after well employing fully automated fluorescence microscopes. Here, we describe an alternative cost-effective optical approach (MULTIPLE) that exploits high-power LED arrays to globally illuminate a culture plate and an sCMOS sensor for parallel detection of the fluorescence coming from multiple wells. MULTIPLE combines optical detection of action potentials using a red-shifted voltage-sensitive fluorescent dye (di-4-ANBDQPQ) with optical stimulation, employing optogenetic actuators, to ensure excitation of cardiomyocytes at constant rates. MULTIPLE was first characterized in terms of interwell uniformity of the illumination intensity and optical detection performance. Then, it was applied for probing action potential features in HL-1 cells (i.e., mouse atrial myocyte-like cells) stably expressing the blue light-activatable cation channel CheRiff. Under proper stimulation conditions, we were able to accurately measure action potential dynamics across a 24-well plate with variability across the whole plate of the order of 10%. The capability of MULTIPLE to detect action potential changes across a 24-well plate was demonstrated employing the selective K(v)11.1 channel blocker (E-4031), in a dose titration experiment. Finally, action potential recordings were performed in spontaneous beating human induced pluripotent stem cell derived cardiomyocytes following pharmacological manipulation of their beating frequency. We believe that the simplicity of the presented optical scheme represents a valid complement to sophisticated and expensive state-of-the-art optical systems for high-throughput cardiac electrophysiological investigations.Cardiolog

Early onset effects of single substrate accumulation recapitulate major features of LSD in patient-derived lysosomes.

Lysosome functions mainly rely on their ability to either degrade substrates or release them into the extracellular space. Lysosomal storage disorders (LSDs) are commonly characterized by a chronic lysosomal accumulation of different substrates, thereby causing lysosomal dysfunctions and secretion defects. However, the early effects of substrate accumulation on lysosomal homeostasis have not been analyzed so far. Here, we describe how the acute accumulation of a single substrate determines a rapid centripetal redistribution of the lysosomes, triggering their expansion and reducing their secretion, by limiting the motility of these organelles toward the plasma membrane. Moreover, we provide evidence that such defects could be explained by a trapping mechanism exerted by the extensive contacts between the enlarged lysosomes and the highly intertwined membrane structures of the endoplasmic reticulum which might represent a crucial biological cue ultimately leading to the clinically relevant secondary defects observed in the LSD experimental models and patients

Structural and functional features of choroid epithelium from buffalo brain.

Abstract Choroid plexuses (CPs) play pivotal roles in many processes that establish, survey, and maintain the biochemical and cellular status of the central nervous system (CNS). Changes in the anatomy and physiology of CPs have been linked to several CNS diseases. However, CP structure and function are not definitely known. Here, we report structural and functional features of choroid epithelium from buffalo brain never described before. Mixed with common epithelial cells, two novel cell types were identified by scanning and transmission electron microscopies. The first peculiar cells showed a globular apical portion projecting into the ventricular cavities, and a basal peduncle in direct contact with blood capillaries underlying the epithelium. The second type of cells resulted to be formed by a globular body from which depart numerous processes; these cells, localized deeply in the choroid epithelium, strictly contact neighboring epithelial cells. No synaptic contacts were detected between these cell populations and common epithelial cells. To gain some insight into the functional properties of choroid cells, NADPH diaphorase (NADPHd) and neuronal nitric oxide synthase (nNOS) activities were evaluated. Of interest, whereas a strong NADPHd activity was detected in all cell types of choroid epithelium, nNOS was only detected in the first type of peculiar cells. The presence of nNOS in the CPs was confirmed by Western blotting. These results suggest that nitric oxide may serve as a signal for the regulation of CP multiple functions. Copyright 2007 Wiley-Liss, Inc

SERT and nNOS expression in the choroid plexus of buffalo brain

Serotonin (5-HT) is a well recognized neurotransmitter in the mammalian central nervous system (CNS). It regulates a variety of physiological functions such as sleep, pain, thermoregulation, feeding, sexual behaviour, and mood. An important component of the 5-HT system is the serotonin transporter SERT which regulates 5-HT homeostasis. Nitric oxide (NO) acts as an intercellular messenger in the CNS, and exerts profound effects on the neuroendocrine functions and behaviour. Within neurons, NO is produced by the activity of one of the isoform of NO synthases present in the organism, namely neuronal NO synthase (nNOS). Although a different anatomical distribution of the central neurons synthetizing 5-HT and NO-producing neurons, functional interactions have been demonstrated between the central 5-HT- and NO-generating systems. Recent data indicate that NO may regulate both the intracellular amount of the amine and its intracellular availability by controlling the release and uptake of 5-HT. In this study, we demonstrated the expression of both SERT and nNOS in the choroid plexuses of buffalo brain by scanning electron microscopy (SEM) and biochemical analyses. Our findings may provide some insights into the mechanism by which the choroid plexus specific barrier acts for the regulation of the most basic neural functions