Potential Firing Research Articles

The mitochondrial calcium uniporter inhibitor Ru265 increases neuronal excitability and reduces neurotransmission via off-target effects.

Excitotoxicity due to mitochondrial calcium (Ca2+) overloading can trigger neuronal cell death in a variety of pathologies. Inhibiting the mitochondrial calcium uniporter (MCU) has been proposed as a therapeutic avenue to prevent calcium overloading. Ru265 (ClRu(NH3)4(μ-N)Ru(NH3)4Cl]Cl3) is a cell-permeable inhibitor of the mitochondrial calcium uniporter (MCU) with nanomolar affinity. Ru265 reduces sensorimotor deficits and neuronal death in models of ischemic stroke. However, the therapeutic use of Ru265 is limited by the induction of seizure-like behaviours. We examined the effect of Ru265 on synaptic and neuronal function in acute brain slices and hippocampal neuron cultures derived from mice, in control and where MCU expression was genetically abrogated. Ru265 decreased evoked responses from calyx terminals and induced spontaneous action potential firing of both the terminal and postsynaptic principal cell. Recordings of presynaptic Ca2+ currents suggested that Ru265 blocks the P/Q type channel, confirmed by the inhibition of currents in cells exogenously expressing the P/Q type channel. Measurements of presynaptic K+ currents further revealed that Ru265 blocked a KCNQ current, leading to increased membrane excitability, underlying spontaneous spiking. Ca2+ imaging of hippocampal neurons showed that Ru265 increased synchronized, high-amplitude events, recapitulating seizure-like activity seen in vivo. Importantly, MCU ablation did not suppress Ru265-induced increases in neuronal activity and seizures. Our findings provide a mechanistic explanation for the pro-convulsant effects of Ru265 and suggest counter screening assays based on the measurement of P/Q and KCNQ channel currents to identify safe MCU inhibitors.

Electrophysiological Mechanisms and Validation of Ferritin-Based Magnetogenetics for Remote Control of Neurons.

Magnetogenetics was developed to remotely control genetically targeted neurons. A variant of magnetogenetics uses magnetic fields to activate transient receptor potential vanilloid (TRPV) channels when coupled with ferritin. Stimulation with static or RF magnetic fields of neurons expressing these channels induces Ca2+ transients and modulates behavior. However, the validity of ferritin-based magnetogenetics has been questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Here, we validated the magnetogenetic approach Ferritin-iron Redistribution to Ion Channels (FeRIC) using electrophysiological (Ephys) and imaging techniques. Previously, interference from RF stimulation rendered patch-clamp recordings inaccessible for magnetogenetics. We solved this limitation for FeRIC, and we studied the bioelectrical properties of neurons expressing TRPV4 (nonselective cation channel) and transmembrane member 16A (TMEM16A; chloride-permeable channel) coupled to ferritin (FeRIC channels) under RF stimulation. We used cultured neurons obtained from the rat hippocampus of either sex. We show that RF decreases the membrane resistance (Rm) and depolarizes the membrane potential in neurons expressing TRPV4FeRIC RF does not directly trigger action potential firing but increases the neuronal basal spiking frequency. In neurons expressing TMEM16AFeRIC, RF decreases the Rm, hyperpolarizes the membrane potential, and decreases the spiking frequency. Additionally, we corroborated the previously described biochemical mechanism responsible for RF-induced activation of ferritin-coupled ion channels. We solved an enduring problem for ferritin-based magnetogenetics, obtaining direct Ephys evidence of RF-induced activation of ferritin-coupled ion channels. We found that RF does not yield instantaneous changes in neuronal membrane potentials. Instead, RF produces responses that are long-lasting and moderate, but effective in controlling the bioelectrical properties of neurons.

DEVELOPMENT OF THE INFORMATION PORTAL “KAZGEOWARNING” FOR FORECASTING FIRES ON THE TERRITORY OF KAZAKHSTAN

This article presents the development of an information system tailored for predicting and managing forest fires in Kazakhstan. The system's primary objective is to establish an information portal dedicated to fire forecasting, enhancing the accuracy of predictions and timely warnings. To achieve this, the system focuses on tasks such as predicting the likelihood of forest and steppe fires, monitoring environmental changes in real-time, and visualising the current situation on maps. It also generates comprehensive reports detailing fire risk, available resources, and necessary measures. Users will receive alerts about potential fire threats, facilitating rapid response. The system's data analysis incorporates geographical and climatic factors for precise forecasting. The ultimate goal is to significantly reduce the environmental and economic impact of forest fires in the country, emphasising the creation of a versatile platform for swift emergency response, integrating modern technologies into practical use. The practical significance encompasses improved fire warnings, enhanced safety for both the population and nature, and a reduction in economic losses. The accompanying website serves as a dynamic platform to collect, analyse, and visualise real-time data on disasters and crises, providing users with geographic information, maps, and reports crucial for making informed decisions during emergency situations.

Impact of fire severity on forest structure and biomass stocks using NASA GEDI data. Insights from the 2020 and 2021 wildfire season in Spain and Portugal

Wildfires have been progressively shrinking the C sink capacity of forest accelerating climate change effects on forest biodiversity, especially where megafires are recurrent and of increased frequency such as in the Mediterranean. Data from The Global Ecosystem Dynamics Investigation (GEDI) mission can inform on changes on forest structure to inform on fire impacts on vegetation. In this study, we assessed the performance of GEDI at measuring biomass and structural change from wildfires using the 2020/21 summer fire seasons in Spain and Portugal. The GEDI hybrid-inference method was used to calculate mean and total biomass in pre- and post-fire stages, while GEDI footprint data was further used to explain the fire severity classes derived from optical data. Our results showed the increasing impact of wildfires on biomass stocks and GEDI ecological metrics by increasing fire severity. More than over biomass stocks, severe fires substantially altered trends in structural metrics such as plant area volume density. The integration of GEDI metrics to explain fire severity had an accuracy of 52% considering five severity classes and an accuracy of 69% when considering the three main classes: unburned, moderate and high. Structural metrics from GEDI can be used to improve optical-based fire severity estimates used globally and to evaluate potential fire impacts based on time-series of GEDI tracks as showcased in the study, but also to measure forest recovery between fire seasons. The extension of GEDI is a major support for wildfire mapping efforts, integrated approaches to capture the increasing impact of fire on forest biodiversity and the monitoring of changes in carbon stocks.

Global variation in ecoregion flammability thresholds

Anthropogenic climate change is altering the state of worldwide fire regimes, including by increasing the number of days per year when vegetation is dry enough to burn. Indices representing the percent moisture content of dead fine fuels as derived from meteorological data have been used to assess geographic patterns and temporal trends in vegetation flammability. To date, this approach has assumed a single flammability threshold, typically between 8 and 12%, controlling fire potential regardless of the vegetation type or climate domain. Here we use remotely sensed burnt area products and a common fire weather index calculated from global meteorological reanalysis data to identify and describe geographic variation in fuel moisture as a flammability threshold. This geospatial analysis identified a wide range of flammability thresholds associated with fire activity across 772 ecoregions, often well above or below the commonly used range of values. Many boreal and temperate forests, for example, can ignite and sustain wildfires with higher estimated fuel moisture than previously identified; Mediterranean forests, in contrast, tend to sustain fires with consistently low estimated fuel moisture. Statistical modelling showed that flammability thresholds derived from burnt area are primarily driven by climatological variables, particularly precipitation and temperature. Our analysis also identified complex associations between vegetation structure, fuel types, and climatic conditions highlighting the complexity in vegetation–climate–fire relationships globally. Our study provides a critical, necessary step in understanding and describing global pyrogeography and tracking changes in spatial and temporal fire activity.

Exploring Ca2+ Dynamics in Myelinating Oligodendrocytes through rAAV-Mediated jGCaMP8s Expression in Developing Spinal Cord Organ Cultures.

Oligodendrocytes, the myelin-producing glial cells of the central nervous system (CNS), crucially contribute to myelination and circuit function. An increasing amount of evidence suggests that intracellular calcium (Ca2+) dynamics in oligodendrocytes mediates activity-dependent and activity-independent myelination. Unraveling how myelinating oligodendrocytes orchestrate and integrate Ca2+ signals, particularly in relation to axonal firing, is crucial for gaining insights into their role in the CNS development and function, both in health and disease. In this framework, we used the recombinant adeno-associated virus/Olig001 capsid variant to express the genetically encoded Ca2+ indicator jGCaMP8s, under the control of the myelin basic protein promoter. In our study, this tool exhibits excellent tropism and selectivity for myelinating and mature oligodendrocytes, and it allows monitoring Ca2+ activity in myelin-forming cells, both in isolated primary cultures and organotypic spinal cord explants. By live imaging of myelin Ca2+ events in oligodendrocytes within organ cultures, we observed a rapid decline in the amplitude and duration of Ca2+ events across different in vitro developmental stages. Active myelin sheath remodeling and growth are modulated at the level of myelin-axon interface through Ca2+ signaling, and, during early myelination in organ cultures, this phase is finely tuned by the firing of axon action potentials. In the later stages of myelination, Ca2+ events in mature oligodendrocytes no longer display such a modulation, underscoring the involvement of complex Ca2+ signaling in CNS myelination.

Bank Specialization and Zombie Lending

We study whether banks internalize congestion externalities when lending to zombie firms. We conjecture that banks should be better informed about the presence of zombie firms and the congestion externalities that such firms exert on healthy borrowers in industries where banks are specialized and show that banks’ credit supply to zombie firms relates negatively to their industry specialization. This relation is stronger when congestion externalities are likely to have stronger adverse effects, namely when zombie firms take a higher fraction of resources in the industry or when the industry is geographically more concentrated. Additionally, this relation is weaker in industries with higher asset specificity as zombie firms’ default (and potential asset fire sales) could reduce healthy borrowers’ collateral value. This paper was accepted by Victoria Ivashina, finance. Supplemental Material: The online appendices and data files are available at https://doi.org/10.1287/mnsc.2023.01437 .

Integration of Fire Detection and Personnel Accountability System

Fire incidents in public spaces pose significant risks to life and property. Traditional fire detection systems often suffer from delays and inaccuracies, necessitating the development of advanced solutions. This paper presents a comprehensive system for integrating fire detection and personnel accountability in surveillance scenarios. With the increasing concerns about safety in public spaces, the need for effective systems to detect fires and ensure personnel safety has become paramount. Traditional methods rely on manual intervention or basic sensors, often resulting in delayed or inaccurate alerts. To address these challenges, our system employs advanced image processing and machine learning to enhance safety measures. By analyzing surveillance camera feeds, it detects changes in pixel intensity, smoke patterns, and heat signatures to identify potential fire incidents. Machine learning models, such as convolutional neural networks (CNNs), are trained to accurately classify fire and non-fire regions in video frames. Additionally, the system tracks personnel presence and movement, ensuring accountability within the surveillance area. Modular and scalable, our system integrates seamlessly with existing infrastructure, providing reliable fire detection and personnel monitoring. Experimental results demonstrate its effectiveness, contributing to enhanced safety in public spaces and facilitating prompt emergency responses.

Emergency control of firefighting vehicles based on distributed integer programming

Fire-related emergency vehicle scheduling has always been an important part of autonomous vehicle emergency management. To maintain the fire safety of buildings and reduce the transportation loss of emergency resources, this paper constructs a multi-objective integer planning model for fire emergency resource scheduling, which minimizes the time spent in the transportation of fire materials and considers the transportation needs of potential fire vehicles. The fixed-point iterative algorithm is realized and optimized, and distributed computing is adopted to improve the solving speed. In this paper, the comparison and simulation experiments with Branch and Bound, improved particle swarm optimization and other algorithms are carried out. The results show that the model and the algorithm can effectively deal with the fire emergency vehicle scheduling problem under different simulated fires and multiple fires occurring at the same time, and have certain advantages in numerical stability and convergence speed.

Crosstalk amongst oxytocin and vasopressin synthesizing neurons of the paraventricular nucleus of the hypothalamus increases blood pressure in mice

The paraventricular nucleus of the hypothalamus (PVH) orchestrates neuroendocrine release and autonomic outflow to maintain body fluid homeostasis and cardiovascular function. Emerging evidence supports the notion that neuropeptides synthesized by PVH neurons create paracrine signals that alter physiology and behavior by affecting the activity of neighboring neurons. Here, we test the hypothesis that PVH neurons synthesizing oxytocin (hereafter referred to a PVHOT) create a paracrine signal that regulates blood pressure. Mice with the expression of Cre-recombinase directed to the OT gene were bred that mice that express a CAG-driven LoxP-flanked stop-codon preceding a channelrhodopsin-2 (ChR2) and eYFP fusion gene at the Rosa26 locus. This produced mice expressing only Cre-recombinase (controls) or mice with ChR2-eYFP expression directed to cells that express oxytocin (OT-ChR2). Confocal image analysis found that ~90% of eYFP expressing neurons were also immunolabeled for OT and electrophysiological recordings obtained from these neurons revealed that pulses of blue light elicited the firing of action potentials. These results confirm directed and functional expression of ChR2 within PVHOT. In vivo optogenetic excitation of PVHOT increased blood pressure and decreased heart rate in OT-ChR2 mice relative to controls. Ganglionic blockade with hexamethonium had no effect on the increased blood pressure elicited by optogenetic excitation of PVHOT but it completely abolished the bradycardia that was previously observed. These results suggest that excitation of PVHOT recruits a neuroendocrine signal that promotes vasoconstriction, which elicits the baroreflex to induce bradycardia by engaging the autonomic nervous system. Consistent with this interpretation, optogenetic excitation of PVHOT increased circulating levels of OT; however, the elevated blood pressure persisted after systemic administration of an OT receptor antagonist. Intriguingly, in vitro optogenetic excitation of PVHOT evoked Ca2+ flux in CHO cells expressing OT or vasopressin receptors (V1aR), suggesting that robust firing of PVHOT is followed by local release of OT. Optogenetic excitation of PVHOT augmented firing of neurons of the PVH that synthesize vasopressin and tended to increase circulating levels of this neuropeptide. Remarkably, systemic administration of a V1aR antagonist completely abolished the increase in blood pressure and bradycardia that were previously observed with in vivo optogenetic excitation of PVHOT. Collectively, these results reveal that robust firing of PVHOT creates an oxytocinergic paracrine signal that increases blood pressure by activating V1aR(s) and increasing circulating vasopressin. AHA 23POST1020034 to KE. NHLBI F31HL1162540 to CBH. NHLBI R01HL136595, R35HL150750, R01HL145028 and NCCIH R65AT012142 to ADK & EGK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Selective KCNQ2/3 Potassium Channel Opener ICA069673 Inhibits Excitability in Mouse Vagal Sensory Neurons

The excitability of vagal sensory neurons is abnormally enhanced in inflammatory visceral diseases, contributing to the unproductive and diffcult-to-treat neuronally based symptoms such as non-cardiac chest pain and excessive coughing. Identification of targets and modulators capable of regulating the excitability of vagal sensory neurons may lead to novel therapeutic options. The KCNQ/KV7/M-channel is increasingly recognized as an intrinsic regulator of excitability in neurons, and several neuronal KCNQ2/3-selective M-channel openers have been developed. This study aimed to characterize the effects of one of these KCNQ2/3-selective activators, ICA-069673, on the M-current (IM) in mouse nodose neurons, and to determine its effects on excitability and action potential firings using perforated patch-clamp technique. The results showed that ICA-069673 enhanced IM density, accelerated the activation and delayed the deactivation of M-channels in a concentration-dependent manner. The EC50 of ICA-069673 in enhancing IM determined at -30 mV is 0.52 μM. ICA-069673 at 10 μM shifted the voltage-dependent activation of IM in hyperpolarizing direction by -25.5 ± 4.1 mV (p<0.001) and increased the maximal conductance from 8.1 ± 4.0 to 12.6±7.4 nS/pF (p=0.031). In a total of 48 nodose neurons studied on voltage-clamp mode, ICA-069673 enhanced IM in 41 neurons (~85%). Consistent with its effects on IM, ICA-069673 induced a marked hyperpolarization of resting potential and reduced the input resistance. The hyperpolarizing effect was more pronounced in partially depolarized neurons. Moreover, ICA-069673 caused a 3-fold increase in the minimal amount of depolarizing current needed to evoke an action potential, and significantly limited the action potential firings in response to sustained suprathreshold stimulations. These results indicate that opening KCNQ2/3-mediated M-channels is suffcient to suppress the excitability and enhance spike accommodation in vagal sensory neurons, and provide evidence supporting further investigation into the effcacy of ICA-069673 in normalizing the aberrant vagal visceral nociception. The study is supported by NIH Grant R35HL155671. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Muscle Sympathetic Action Potential Firing Patterns Following Intranasal Insulin Administration in Healthy Adults

Objective: Systemic insulin increases muscle sympathetic nervous system activity (MSNA) in healthy adults by augmenting firing frequency of medium-sized sympathetic action potentials (AP) and recruiting previously latent, larger axons. Whether these neural coding patterns are due to central or peripheral effects of insulin is unclear. We examined the impact of elevated central insulin on AP firing patterns in healthy adults. We hypothesized intranasal insulin administration, which increases central insulin levels, would increase MSNA via elevated firing frequency of APs and recruitment of previously latent, larger axons. Methods: Ten participants were assigned to time control [TC, n=6 (3M/3F)] or 160 IU of intranasal insulin [n=4 (3M/1F)] administered over 5 min. MSNA (fibular microneurography) was assessed at baseline and for 30 min following insulin administration. Sympathetic APs were identified using a matched mother wavelet and continuous wavelet transform. APs were divided into the proportion of those firing in small, medium, or large amplitude clusters. AP firing frequency, percent of APs firing within an MSNA burst (synchronous), and the probability of clusters firing more than once within an MSNA burst were identified. Data are reported as median (interquartile range). Results: MSNA burst frequency increased 15 min after intranasal insulin administration [24(20) to 31(23) bursts/min, p=0.03]. At this time, the percent of synchronous APs [72(27) to 90(24)%, p=0.02] and the probability of medium-sized AP clusters firing more than once within an MSNA burst [13(14) to 19(17)%, p=0.03] increased. No changes in MSNA burst frequency [23(14) to 25(13) bursts/min, p=0.27], percent of synchronous APs [74(15) to 75(34), p=0.48], nor firing probability of medium-sized AP clusters [6(12) to 8(7)%, p=0.97] occurred in TC. The total number of detected clusters did not change in either group (p>0.05). Conclusions: Intranasal insulin increases MSNA burst frequency due to a higher percent of synchronous APs, particularly medium-sized AP clusters; however, we did not observe recruitment of latent, larger axons. These exploratory data highlight potential differences in the sympathetic response to central versus peripheral insulin exposure in healthy adults. CAFNR Joy of Discovery (JKL, JP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

DESIGN OF A FIRE DETECTION SYSTEM USING FIRE AND SMOKE SENSORS BASED ON ARDUINO MICROCONTROLLER

Fires very often occur due to gas leaks, careless throwing of cigarette butts or electrical short circuits which result in the fire getting bigger, causing a lot of losses. Many fire cases are discovered when the fire has already occurred and few can be detected from the start. The research aims to develop an effective system for detecting fires by integrating fire and smoke sensors, as well as providing notifications via the Blynk platform. This research is research and development (R&D) using a prototype development model. The results of the functionality testing obtained a 100% presentation which shows that the prototype is suitable for use. Tests were carried out using three levels of fire levels and various distances, showing good response from the fire sensor with a consistent incoming notification speed of around 2-3 seconds. The results of fire measurements using the MQ-2 smoke sensor show accuracy in detecting smoke concentration levels, with timely notification of potential fires. This research has produced a detection tool that has the ability to detect early fire in a room which can provide warning notifications that are integrated with Internet of Things (IoT).

Retromer- and Retriever-Associated Sorting Nexins Regulate Traffcking of KCa2.3 Channels

Correct function of the Ca2+-activated K+ channel KCa2.3 (SK3) is essential for several physiological processes. Activity of KCa2.3 in neurons modulates the rate of action potential firing; in endothelial cells activation of KCa2.3 channels induces vasodilation, and accordingly, a decrease in blood pressure. KCa2.3 activity (i.e. currents) can be modulated by two main variables: the open probability ( Po) and the number of channels inserted into the plasma membrane ( N). Numerous pharmacological compounds have been identified and developed to alter KCa2.3 Po. In contrast, the mechanisms that control delivery of KCa2.3 to and from the plasma membrane are still poorly understood. After endocytosis, plasma membrane proteins are targeted to the endosomal network which is a key area for sorting membrane-bound proteins. Several endosomal-associated coat complexes have been identified that ‘rescue’ proteins from degradation and sequester proteins into recycling tubules for transport back to the plasma membrane. These complexes include Retromer, Retriever, and Commander. Associated with these complexes are members of the Sorting Nexin (SNX) family. SNX proteins bind to specific amino acid motifs to sort proteins for Retromer- or Retriever-mediated recycling. Interestingly, the Devor laboratory has demonstrated KCa2.3 can be rapidly recycled back into the plasma membrane after endocytosis. Based on those data, we hypothesised that the Retromer and Retriever complexes regulate KCa2.3 recycling. To investigate this, we are using biochemical [e.g. cell surface biotinylation, co-immunoprecipitation (co-IP)] and electrophysiological (e.g. patch-clamp) techniques. First, we determined the role of SNXs in KCa2.3 traffcking by using siRNA to knock down SNX protein expression in Fisher rat thyroid (FRT) cells expressing heterologous KCa2.3. Knockdown of Retromer-associated SNX3 or Retriever-associated SNX17 significantly decreased the cell surface population of KCa2.3 ( P<0.01, n=4, each). With protein-protein interaction experiments, KCa2.3 co-IPed with SNX17 and SNX3, but not Retromer-associated SNX27 ( n=3, each). Electrophysiology experiments are underway to determine if the knockdown of SNXs alters the functional expression of KCa2.3. and We are also investigating if KCa2.3 traffcking in primary endothelial cells requires SNX3 and SNX17. These results suggest that SNX3 and SNX17 are novel regulators of KCa2.3 traffcking. This work was supported by grants from NIH (HL083060, HL092157) and the Cystic Fibrosis Foundation (DEVOR20GO) to D.C.D.; Lottery Health New Zealand (R-LHR-2019-101706) to F.J.M.; and Aim Fund grant to K.L.H., and the Department of Physiology, University of Otago. M.J.E.L. was supported by a doctoral scholarship from the University of Otago. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prototype of Automatic Door and Fire Alarm System Based on IoT

This research discusses the development of a prototype of an automatic door and fire alarm system based on the Internet of Things (IoT) utilizing IR sensors to detect people, servo motors to automate door opening, flame detectors for fire detection, MQ-2 sensors for smoke detection, and Telegram as a notification medium. The integration of these technologies aims to enhance security and automation in home or office environments. IR sensors are used to detect people approaching the door, while servo motors provide a solution for door automation. Flame detectors and MQ-2 are employed to detect potential fires by issuing early warnings. This system communicates through the Telegram application to notify users. Testing conducted indicates that IR sensors can detect the presence of people up to a distance of 5cm to activate the micro servo opening the door. The flame detector effectively detects fire up to a distance of 30cm, while the MQ-2 sensor detects smoke up to a distance of 20cm; both generate output signals to activate the micro servo, LED, and buzzer for fire alarms, as well as sending notifications via Telegram to the building owner. With this approach, it is hoped to create an effective, efficient, and reliable system to enhance security and response to emergency situations.

Nanoactuator for Neuronal Optoporation.

Light-driven modulation of neuronal activity at high spatial-temporal resolution is becoming of high interest in neuroscience. In addition to optogenetics, nongenetic membrane-targeted nanomachines that alter the electrical state of the neuronal membranes are in demand. Here, we engineered and characterized a photoswitchable conjugated compound (BV-1) that spontaneously partitions into the neuronal membrane and undergoes a charge transfer upon light stimulation. The activity of primary neurons is not affected in the dark, whereas millisecond light pulses of cyan light induce a progressive decrease in membrane resistance and an increase in inward current matched to a progressive depolarization and action potential firing. We found that illumination of BV-1 induces oxidation of membrane phospholipids, which is necessary for the electrophysiological effects and is associated with decreased membrane tension and increased membrane fluidity. Time-resolved atomic force microscopy and molecular dynamics simulations performed on planar lipid bilayers revealed that the underlying mechanism is a light-driven formation of pore-like structures across the plasma membrane. Such a phenomenon decreases membrane resistance and increases permeability to monovalent cations, namely, Na+, mimicking the effects of antifungal polyenes. The same effect on membrane resistance was also observed in nonexcitable cells. When sustained light stimulations are applied, neuronal swelling and death occur. The light-controlled pore-forming properties of BV-1 allow performing "on-demand" light-induced membrane poration to rapidly shift from cell-attached to perforated whole-cell patch-clamp configuration. Administration of BV-1 to ex vivo retinal explants or in vivo primary visual cortex elicited neuronal firing in response to short trains of light stimuli, followed by activity silencing upon prolonged light stimulations. BV-1 represents a versatile molecular nanomachine whose properties can be exploited to induce either photostimulation or space-specific cell death, depending on the pattern and duration of light stimulation.

Electrophysiology and 3D-imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation.

Altered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown. Here we have addressed this knowledge gap in human GP neuron structure and physiology in patients with and without AF. Human right atrial GP neurons embedded in epicardial adipose tissue were excised during open heart surgery performed on both non-AF and AF patients and then characterised physiologically by whole cell patch clamp techniques. Structural analysis was also performed after fixation at both the single cell and at the entire GP levels via three-dimensional confocal imaging. Human GP neurons were found to exhibit unique properties and structural complexity with branched neurite outgrowth. Significant differences in excitability were revealed between AF and non-AF GP neurons as measured by lower current to induce action potential firing, a reduced occurrence of low action potential firing rates, decreased accommodation and increased synaptic density. Visualisation of entire GPs showed almost all neurons are cholinergic with a small proportion of noradrenergic and dual phenotype neurons. Phenotypic distribution differences occurred with AF including decreased cholinergic and dual phenotype neurons, and increased noradrenergic neurons. These data show both functional and structural differences occur between GP neurons from patients with and without AF, highlighting that cellular plasticity occurs in neural input to the heart that could alter autonomic influence on atrial function. KEY POINTS: The autonomic nervous system plays a critical role in regulating heart rhythm and the initiation of AF; however, the structural and functional properties of human autonomic neurons in the autonomic ganglionated plexi (GP) remain unknown. Here we perform the first whole cell patch clamp electrophysiological and large tissue confocal imaging analysis of these neurons from patients with and without AF. Our data show human GP neurons are functionally and structurally complex. Measurements of action potential kinetics show higher excitability in GP neurons from AF patients as measured by lower current to induce action potential firing, reduced low firing action potential rates, and decreased action potential accommodation. Confocal imaging shows increased synaptic density and noradrenergic phenotypes in patients with AF. Both functional and structural differences occur in GP neurons from patients with AF that could alter autonomic influence on atrial rhythm.

Integrating IOT and Drone Technology for Real-Time Forest Monitoring and Fire Detection: A Sustainable Approach for Ecosystem Preservation

This paper proposes an innovative approach to address the pressing challenges of forest monitoring and fire detection by leveraging the synergistic capabilities of Internet of Things (IOT) devices and drones. By integrating these cutting-edge technologies, our approach aims to revolutionize traditional forest management practices by facilitating real-time data collection, analysis, and decision-making. Through the strategic deployment of IOT sensors across forested areas, we can gather comprehensive environmental data, including temperature, humidity, air quality, and vegetation health. This extensive dataset, combined with the aerial surveillance capabilities of drones equipped with thermal imaging cameras, enables early detection and rapid response to potential fire incidents .Moreover, the proposed approach holds significant potential for enhancing collaboration and coordination among stakeholders involved in forest management, including government agencies, environmental organizations, and local communities. By providing access to timely and accurate information, it fosters greater transparency, accountability, and stakeholder engagement in decision-making processes related to forest conservation and sustainability. In conclusion, our innovative approach to forest monitoring and fire detection represents a paradigm shift in ecosystem management, offering a powerful toolkit for preserving biodiversity, mitigating climate change, and promoting sustainable forestry practices. Through continued research, development, and implementation, we can harness the full potential of IOT and drone technology to safeguard our forests for future generations. Keywords - Internet of Things (IOT), Drones, Environmental sensors, Data analytics, Sustainable forestry

Electrophysiological properties of dorsal root ganglion neurons cultured on 3D silicon micro-pillar substrates

BackgroundSilicon-based micro-pillar substrates (MPS), as three-dimensional cell culture platforms with vertically aligned micro-patterned scaffolding structures, are known to facilitate high-quality growth and morphology of dorsal root ganglion (DRG) sensory neurons, promote neurite outgrowth and enhance neurite alignment. However, the electrophysiological aspects of DRG neurons cultured on silicon MPSs have not been thoroughly investigated, which is of greatest importance to ensure that such substrates do not disrupt neuronal homeostasis and function before their widespread adoption in diverse biomedical applications. New methodWe conducted whole-cell patch-clamp recordings to explore the electrophysiological properties of DRG neurons cultured on MPS arrays, utilizing a custom-made upright patch-clamp setup. ResultsOur findings revealed that DRG neurons exhibited similar electrophysiological responses on patterned MPS samples when compared to the control planar glass surfaces. Notably, there were no significant differences observed in the action potential parameters or firing patterns of action potentials between neurons grown on either substrate. Comparison with existing methodsIn the current study we for the first time confirmed that successful electrophysiological recordings can be obtained from the cells grown on MPS. ConclusionOur results imply that, despite the potential alterations caused by the cumulative trauma of tissue harvest and cell dissociation, essential functional cell properties of DRG neurons appear to be relatively maintained on MPS surfaces. Therefore, vertically aligned silicon MPSs could be considered as a potentially effective three-dimensional system for supporting a controlled cellular environment in culture.

Single-Cell Model of Orexin Neuron and Adaptive Glucose-sensing Mechanism

Orexin neurons are critical for regulating sleep-wake behavior. Their intrinsic firing activity promotes wakefulness. Orexin neurons are also specialized sensor of the body’s glucose level. Small rises in glucose level inhibit intrinsic action potential firing of orexin neuron. A distinct group of orexin neuron exhibits only transient inhibitory responses to sustained glucose stimulation. This adaptation involves recovery from inhibition via closure of leak-like potassium channels. In this project, we simulated the baseline behavior and adapting/nonadapting orexin response to sustained glucose stimulation in MatLab environment.