Explore the vast range of titles available.

Ca2+ concentrations drop rapidly over a distance of a few tens of nanometers from an open voltage-gated Ca2+ channel (Cav), thereby, generating a spatially steep and temporally short-lived Ca2+ gradient that triggers exocytosis of a neurotransmitter filled synaptic vesicle. These non-steady state conditions make the Ca2+-binding kinetics of the Ca2+ sensors for release and their spatial coupling to the Cavs important parameters of synaptic efficacy. In the mammalian central nervous system, the main release sensors linking action potential mediated Ca2+ influx to synchronous release are Synaptotagmin (Syt) 1 and 2. We review here quantitative work focusing on the Ca2+ kinetics of Syt2-mediated release. At present similar quantitative detail is lacking for Syt1-mediated release. In addition to triggering release, Ca2+ remaining bound to Syt after the first of two successive high-frequency activations was found to be capable of facilitating release during the second activation. More recently, the Ca2+ sensor Syt7 was identified as additional facilitation sensor. We further review how several recent functional studies provided quantitative insights into the spatial topographical relationships between Syts and Cavs and identified mechanisms regulating the sensor-to-channel coupling distances at presynaptic active zones. Most synapses analyzed in matured cortical structures were found to operate at tight, nanodomain coupling. For fast signaling synapses a developmental switch from loose, microdomain to tight, nanodomain coupling was found. The protein Septin5 has been known for some time as a developmentally down-regulated ‘inhibitor’ of tight coupling, while Munc13-3 was found only recently to function as a developmentally up-regulated mediator of tight coupling. On the other hand, a highly plastic synapse was found to operate at loose coupling in the matured hippocampus. Together these findings suggest that the coupling topography and its regulation is a specificity of the type of synapse. However, to definitely draw such conclusion our knowledge of functional active zone topographies of different types of synapses in different areas of the mammalian brain is too incomplete.

Tobacco (nicotine) has been reported as one of the worst global public health pandemics in history, claiming about 8 million lives annually. According to the World Health Organisation (WHO), nicotine accounts for about 7 million deaths of firsthand users and over 1.3 million morbidities of secondhand users. Furthermore, smokeless tobacco products have been linked to more than 300 million morbidities, including chronic kidney illnesses. On the basis of this trend, a possible increase of over 100% in mortality rate and a state of emergency have been predicted from now till 2050. However, electrochemical analysis has demonstrated cost‐effective and easily synthesised sensors as a timely alternative for the rapid analysis and quantification of nicotine in diverse products. A carbon‐based silver sensor was fabricated and characterised by energy‐dispersive x‐ray (EDX) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), direct light scattering (DLS), and x‐ray diffraction (XRD). Herein, we report the first electrochemical detection, release monitoring and quantification of conjugated nicotine. The sensor showed a significant sensitivity, specificity and discriminating power with a detection and quantification limit of 2.283 × 10−9 and 0.761 × 10−8 M, respectively. An average recovery rate of 96.26% was recorded. The applicability of the modified electrode was examined in human urine and serum. The research showed the potential of this method for monitoring doping and nicotine release, as well as for diagnostic and quality control purposes.

A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release. The nervous system sends information around the body in the form of electrical signals that travel through cells called neurons. However, these electrical signals cannot cross the synapses between neurons. Instead, the information is carried across the synapse by molecules called neurotransmitters. Calcium ions control the release of neurotransmitters. There is a high concentration of calcium ions outside the neuron but they are not able to pass through the cell membrane under normal conditions. However, when an electrical impulse reaches the synapse, ion channels in the membrane open and allow calcium ions to enter the cell. Once inside, the ions activate the release of neurotransmitters by binding to proteins called release sensors. Several experiments on the release of neurotransmitters have studied the synapses between neurons and muscle fibers. These studies found that the higher the concentration of ions outside the neuron, the higher the rate at which the neurotransmitters were released. However, the timing of release—the length of time over which the neurotransmitters were released—did not depend on the concentration of calcium ions. Arai and Jonas have now studied neurotransmitter release at a synapse in a region of the brain called the cerebellum. These experiments also found that the timing of the release did not depend on the ion concentration, suggesting that this may be a general property of neurotransmitter release. To find out more, Arai and Jonas created a mathematical model of neurotransmitter release. This model suggests that for the timing of release to remain the same, the ion channel and the release sensor must be located close together in the presynaptic terminal. If they are not close together, the timing of release becomes blurred and more dependent on the external calcium concentration. Further experiments confirm the prediction of the model by showing that the calcium channels and the release sensors in these synapses are very close together. The next challenge will be to find out whether the conclusions are also valid for other synapses where the calcium channels and release sensors are further apart.

In the work at hand, a shape memory alloy (SMA)-based system is presented. The system, conceived for releasing environmental sensors from ground or small unmanned aerial vehicles, UAV (often named UAS, unmanned aerial system), is made of a door, integrated into the bottom of the fuselage, a device distributor, operated by a couple of antagonistic SMA springs, and a kinematic chain, to synchronize the deployment operation with the system movement. On the basis of the specifications (weight, available space, energy supply, sensors size, etc.), the system design was addressed. After having identified the main system characteristics, a representative mock-up was manufactured, featuring the bottom part of the reference fuselage. Functionality tests were performed to prove the system capability to release the sensors; a detailed characterization was finally carried out, mainly finalized at correlating the kinematic chain displacement with the SMA spring temperature and the supplied electrical power. A comparison between theoretical predictions and experimental outcomes showed good agreement.

In cardiomyocytes, intracellular calcium (Ca2+) transients are elicited by electrical and receptor stimulations, leading to muscle contraction and gene expression, respectively. Although such elevations of Ca2+levels ([Ca2+]) also occur in the nucleus, the precise mechanism of nuclear [Ca2+] regulation during different kinds of stimuli, and its relationship with cytoplasmic [Ca2+] regulation are not fully understood. To address these issues, we used a new region-specific fluorescent protein-based Ca2+ indicator, GECO, together with the conventional probe Fluo-4 AM. We confirmed that nuclear Ca2+ transients were elicited by both electrical and receptor stimulations in neonatal mouse ventricular myocytes. Kinetic analysis revealed that electrical stimulation-elicited nuclear Ca2+ transients are slower than cytoplasmic Ca2+ transients, and chelating cytoplasmic Ca2+ abolished nuclear Ca2+ transients, suggesting that nuclear Ca2+ are mainly derived from the cytoplasm during electrical stimulation. On the other hand, receptor stimulation such as with insulin-like growth factor-1 (IGF-1) preferentially increased nuclear [Ca2+] compared to cytoplasmic [Ca2+]. Experiments using inhibitors revealed that electrical and receptor stimulation-elicited Ca2+ transients were mainly mediated by ryanodine receptors and inositol 1,4,5-trisphosphate receptors (IP3Rs), respectively, suggesting different mechanisms for the two signals. Furthermore, IGF-1-elicited nuclear Ca2+ transient amplitude was significantly lower in myocytes lacking neuronal Ca2+ sensor-1 (NCS-1), a Ca2+ binding protein implicated in IP3R-mediated pathway in the heart. Moreover, IGF-1 strengthened the interaction between NCS-1 and IP3R. These results suggest a novel mechanism for receptor stimulation-induced nuclear [Ca2+] regulation mediated by IP3R and NCS-1 that may further fine-tune cardiac Ca2+ signal regulation.

Neuropeptide Y (NPY) is an abundantly expressed peptide in the nervous system. Its widespread distribution along with its receptors, both centrally and peripherally, indicates its broad functions in numerous biological processes. However, the low endogenous concentration and diffuse distribution of NPY make it challenging to study its actions and dynamics directly and comprehensively. Studies on the role of NPY have primarily been limited to exogenous application, transgene expression, or knock-out in biological systems, which are often combined with pharmacological probes to delineate the involvement of specific NPY receptors. Therefore, to better understand the function of NPY in time and space, direct visualization of the real-time dynamics of endogenous NPY is a valuable and desired tool. Using the first-generation and newly developed intensiometric green fluorescent G-protein-coupled NPY sensor (GRAB NPY1.0), we, for the first time, demonstrate and characterize the direct detection of endogenously released NPY in cultured cortical neurons. A dose-dependent fluorescent signal was observed upon exogenous NPY application in nearly all recorded neurons. Pharmacologically evoked neuronal activity induced a significant increase in fluorescent signal in 32% of neurons, reflecting the release of NPY, despite only 3% of all neurons containing NPY. The remaining pool of neurons expressing the sensor were either non-responsive or displayed a notable decline in the fluorescent signal. Such decline in fluorescent signal was not rescued in cortical cultures transduced with an NPY overexpression vector, where 88% of the neurons were NPY-positive. Overexpression of NPY did, however, result in sensor signals that were more readily distinguishable. This may suggest that biological factors, such as subtle changes in intracellular pH, could interfere with the fluorescent signal, and thereby underestimate the release of endogenous NPY when using this new sensor in its present configuration. However, the development of next-generation NPY GRAB sensor technology is expected soon, and will eventually enable much-wanted studies on endogenous NPY release dynamics in both cultured and intact biological systems.

A multifunctional polyvinyl alcohol (PVA) film integrated with a Metronidazole.hydrogen-bonded organic framework (MET.HOF) encapsulating metronidazole was developed. The stability of MET.HOF is to temperature and pH-sensitive variations, leading to the controlled release of metronidazole under such conditions. Additionally, the incorporation of anthocyanin into the polymer matrix imparts the ability to detect ammonia, as anthocyanin exhibits color changes in response to pH fluctuations. Consequently, this film serves as a temperature/pH-responsive smart wound dressing. To assess the drug release behavior, the film’s responsiveness was tested at different pH levels (5.5, 7.4, and 9) and temperatures (37 °C and 40 °C), conditions representative of wound environments. The results demonstrated that the polymer film effectively released metronidazole at temperatures above 37 °C and under alkaline pH, allowing for tailored drug delivery based on wound conditions. Anthocyanin functioned as a natural pH indicator, enabling the detection of ammonia produced at infected wound sites. The polymer’s color change was quantitatively analyzed using RGB color detection software, with a minimum detectable concentration of 1.25 ± 0.07 mg L −1 . The film exhibited a contact angle of 58.8° ± 4.2° and a swelling degree of 240% ± 50%. Antibacterial tests revealed a zone of inhibition of 10 mm ± 1 at a concentration of 50 mg mL −1 , with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) both at 500 μg mL −1 . The polymer also demonstrated significant antioxidant activity, ranging from 85.90 to 97.00%. The study introduces a novel factor influencing crystal growth in hydrogen-bonded organic framework structures.

Flexible micro-sensors have significant application potential in the field of sports performance evaluation. The aim of this study is to assess sports performance by grip pressure using a MMSS sensor (MXene as the sensitive material and melamine sponge as the substrate, a type of flexible piezoresistive pressure sensor). The grip pressures of expert and amateur players are evaluated in single skills events (golf, billiards, basketball, javelin and shot put) and in skills conversion (badminton and tennis). Indicators (time nodes, intervals, peaks, etc.) related to grip pressure on the handle are collected, analyzed, and identified by artificial intelligence. Finally, the K-Nearest Neighbor (KNN) of artificial intelligence algorithms is employed to identify differences for 400 strokes of tennis players in interval training session. Expert tennis athlete exhibits a higher level of precision, concentration and stability for exert and release of grip force (KNN accuracy of train 95.0%) than amateur (KNN: 84.6%) during single movement, technical conversion, and interval training condition. This research offers a new perspective for evaluating sports performance in hand-held equipment events and presents a feasible direction for facing challenges of flexible wearable technology in practice.

Nuclear security is a critical concept for public health, counter-terrorism efforts, and national security. Nuclear radioactive materials should be monitored and secured in near real-time to reduce potential danger of malicious usage. However, several challenges have arose to detect the anomalous radioactive source in a large geographical area. Radiation naturally occurs in the environment. Therefore, a non-zero level of radiation will always exist with or without an anomalous radioactive source present. Additionally, radiation data contain high levels of uncertainty, meaning that the measured radiation value is significantly affected by the velocity of the detector and background noise. In this article, we propose an innovative approach to detect anomalous radiation source using mobile sensor networks combined with a Poisson kriging technique. We validate our results using several experiments with simulated radioactive sources. As results, the accuracy of the model is extremely high when the source intensity is high or the anomalous source is close enough to the detector.

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.