Elevated Firing Research Articles

Modeling seizure networks in neuron-glia cultures using microelectrode arrays.

Epilepsy is a common neurological disorder, affecting over 65 million people worldwide. Unfortunately, despite resective surgery, over 30 of patients with drug-resistant epilepsy continue to experience seizures. Retrospective studies considering connectivity using intracranial electrocorticography (ECoG) obtained during neuromonitoring have shown that treatment failure is likely driven by failure to consider critical components of the seizure network, an idea first formally introduced in 2002. However, current studies only capture snapshots in time, precluding the ability to consider seizure network development. Over the past few years, multiwell microelectrode arrays have been increasingly used to study neuronal networks in vitro. As such, we sought to develop a novel in vitro MEA seizure model to allow for study of seizure networks. Specifically, we used 4-aminopyridine (4-AP) to capture hyperexcitable activity, and then show increased network changes after 2days of chronic treatment. We characterize network changes using functional connectivity measures and a novel technique using dimensionality reduction. We find that 4-AP successfully captures persistently elevated mean firing rate and significant changes in underlying connectivity patterns. We believe this affords a robust in vitro seizure model from which longitudinal network changes can be studied, laying groundwork for future studies exploring seizure network development.

Distentanging the late-Holocene human–environment interactions in the Altai Mountains within the Arid Central Asia

Understanding the impacts of human activities on landscapes necessitates a comprehensive analysis of historical changes in climate, vegetation, fire and land utilization. The human-environment interactions were investigated through the analysis of new charcoal data from Kelashazi Peat in the Altai Mountains, compared with the detailed paleoenvironmental records and historical human activities (e.g., agriculture and pastoralism) at other three distinct sites. The findings suggest that the late-Holocene (prior to ∼2000 years ago) fire activities were mainly influenced by temperature at higher elevations and were primarily driven by vegetation cover at lower elevations. Over the past two millennia, human activities have increasingly impacted fire dynamics. Elevated fire frequencies during the Medieval Warm Period at higher elevations were linked to warmer climates and intensified pastoral activities. Lower fire incidences at lower elevations may be attributed to population outflows during the Medieval Warm Period, while heightened fire occurrences at lower elevations might result from increasing agricultural activities during the Little Ice Age. This study underscores the intricate interplay between natural climate-vegetation-fire dynamics and anthropogenic burning trends in the late Holocene across different elevations of the Altai Mountains within the Arid Central Asia.

Dentate gyrus granule cells are a locus of pathology in Scn8a developmental encephalopathy

Gain-of-function mutations in SCN8A cause developmental and epileptic encephalopathy (DEE), a disorder characterized by early-onset refractory seizures, deficits in motor and intellectual functions, and increased risk of sudden unexpected death in epilepsy. Altered activity of neurons in the corticohippocampal circuit has been reported in mouse models of DEE. We examined the effect of chronic seizures on gene expression in the hippocampus by single-nucleus RNA sequencing in mice expressing the patient mutation SCN8A-p.Asn1768Asp (N1768D). One hundred and eighty four differentially expressed genes were identified in dentate gyrus granule cells, many more than in other cell types. Electrophysiological recording from dentate gyrus granule cells demonstrated an elevated firing rate. Targeted reduction of Scn8a expression in the dentate gyrus by viral delivery of an shRNA resulted in doubling of median survival time from 4 months to 8 months, whereas delivery of shRNA to the CA1 and CA3 regions did not result in lengthened survival. These data indicate that granule cells of the dentate gyrus are a specific locus of pathology in SCN8A-DEE.

A potentiation of REM sleep-active neurons in the lateral habenula may be responsible for the sleep disturbance in depression

Psychiatric disorders with dysfunction of the lateral habenula (LHb) show sleep disturbance, especially a disinhibition of rapid eye movement (REM) sleep in major depression. However, the role of LHb in physiological sleep control and how LHb contributes to sleep disturbance in major depression remain elusive. Here, we found that functional manipulations of LHb glutamatergic neurons bidirectionally modulated both non-REM (NREM) sleep and REM sleep. Activity recording revealed heterogeneous activity patterns of LHb neurons across sleep/wakefulness cycles, but LHb neurons were preferentially active during REM sleep. Using an activity-dependent tagging method, we selectively labeled a population of REM sleep-active LHb neurons and demonstrated that these neurons specifically promoted REM sleep. Neural circuit studies showed that LHb neurons regulated REM sleep via projections to the ventral tegmental area but not to the rostromedial tegmental nucleus. Furthermore, we found that the increased REM sleep in a depression mouse model was associated with a potentiation of REM sleep-active LHb neurons, including an increased proportion, elevated spike firing, and altered activity mode. Importantly, inhibition of REM sleep-active LHb neurons not only attenuated the increased REM sleep but also alleviated depressive-like behaviors in a depression mouse model. Thus, our results demonstrated that REM sleep-active LHb neurons selectively promoted REM sleep, and a potentiation of these neurons contributed to depression-associated sleep disturbance.

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.

Propagation of NO2 originated in intense fires in the Paraná River Delta analyzed from satellite observations

Wildfires in the Paraná River Delta started to be a common situation in the year 2008 and during the first years of the 2020́s decade: 2020, 2021, 2022. These fires affected natural areas, primarily the islands within the delta, situated in front of Rosario city (32.95 °S, 60.67 °W, 25 meters above sea level (m.a.s.l.)), Argentina. They mostly occur during the period between June and September each year and are more intense when a strong La Niña event is present. The aim of this study is to examine the association between the propagation of high intensity nitrogen dioxide (NO2) plumes and the significant fire events that occurred in the Paraná River Delta from 6 to 17 September 2022. Satellite data of NO2 obtained from the TROPOspheric Monitoring Instrument (TROPOMI) on board the European Space Agency (ESA) Sentinel-5 Precursor satellite, air mass forward trajectories performed with The Hybrid Single-Particle Lagrangian Integrated Trajectory model (HYSPLIT), Fire Radiative Power (FRP) data provided by Visible Infrared Imaging Radiometer Suite (VIIRS) on board The National Oceanic and Atmospheric Administration - 20 (NOAA-20) and Suomi National Polar-orbiting Partnership (S-NPP) satellites, Aerosol Optical Depth (AOD) from VIIRS S-NPP and Smoke Injection Height from Multi-Angle Implementation of Atmospheric Correction (MAIAC) Thermal Technique were employed. The trajectories followed by the air masses coming from the major fire sources locations nearby Rosario city and its surrounding area, were analyzed at altitudes of 20, 500, 1000, 1500 and 2000 m above ground level (AGL) in order to evaluate the impact of the NO2 clouds present in the atmosphere and carried by the winds, at different sites of Rosario and its adjacent region. The NO2 plumes has the potential to pose a significant health risk for this region, inhabited by an approximate population of one and a half million individuals. This risk is contingent upon the altitude where the highest levels of NO2 in the tropospheric column are found. Tropospheric vertical column densities (VCDs) of NO2 in the range of 4.68×1014 to 1.66×1016 molecules/cm2 were determined. The results indicate a robust correlation between elevated tropospheric NO2 VCD values and intense fires, as characterized by their FRP. Additionally, high tropospheric NO2 VCDs were observed to impact cities and towns located in close proximity to the fires. In particular, the unusually high tropospheric NO2 VCDs determined for the towns of Fighiera and Pueblo Esther, situated along the coast and near the Paraná River Delta, are noteworthy. This is uncommon considering they are small towns in rural areas that typically have good air quality. The results regarding FRP, provided by VIIRS on board NOAA-20 and S-NPP satellites, indicate that the fire characterization of hotspots during the considered period had a mean value in the range of 20.17–21.47 MW. On specific days (12, 13 and 16 September 2022), the cumulative (total) daily values were very high, ranging from 2000 to 10000 MW. Furthermore, on 12 and 13 September 2022, the smoke aerosols did not reach significant altitudes in the atmosphere, remaining within the range of 0 to 1500 m AGL. During the fire period, AOD values close to 1 were observed within the fire plume. Notably, Puerto San Martín (0.27), San Lorenzo (0.22), and Ibarlucea (0.20) recorded higher average AOD values compared to other sites. The remaining sites generally exhibited lower average AOD values, with a slight distinction between rural locations (Pueblo Esther: 0.14 and Fighiera: 0.14) and the city center of Rosario (0.09).

Experimental study on reinforced concrete beams strengthened with Basalt and Carbon Textile Reinforced mortars at elevated temperatures

Reinforced concrete members strengthened with Fibre-Reinforced Polymer will suffer degradation when exposed to elevated temperatures or fire without an external insulation. Textile Reinforced Mortars (TRMs) can alleviate these problems posed by Fibre Reinforced Polymer epoxies at elevated temperatures. The present study deals with the thermo-mechanical behaviour of reinforced concrete beams strengthened with Textile Reinforced Mortar at elevated temperatures. Reinforced concrete beams were strengthened with Basalt and Carbon textiles and tested while the specimens were maintained in hot conditions. Carbon and Basalt TRMs were applied as one-layer and one- and three-layer, respectively. All the test specimens were heated to 200 °C, 400 °C, 600 °C, and 800 °C, followed by mechanical loading to evaluate their flexural behaviours. Strengthened members experienced common degradation of flexural strength when subjected to higher temperatures except at 400 °C. The test results revealed that Textile Reinforced Mortars can sustain temperatures up to 600 °C, but the concrete and steel underwent degradation at this temperature. At 800 °C, the Basalt textile showed signs of annealing, whereas the carbon textile oxidised from the textile reinforced mortar matrix. The study also evaluated strengthened members' thermal response and mechanical failure patterns at elevated temperatures.

Neural and behavioural state switching during hippocampal dentate spikes

Distinct brain and behavioural states are associated with organized neural population dynamics that are thought to serve specific cognitive functions1–3. Memory replay events, for example, occur during synchronous population events called sharp-wave ripples in the hippocampus while mice are in an ‘offline’ behavioural state, enabling cognitive mechanisms such as memory consolidation and planning4–11. But how does the brain re-engage with the external world during this behavioural state and permit access to current sensory information or promote new memory formation? Here we found that the hippocampal dentate spike, an understudied population event that frequently occurs between sharp-wave ripples12, may underlie such a mechanism. We show that dentate spikes are associated with distinctly elevated brain-wide firing rates, primarily observed in higher order networks, and couple to brief periods of arousal. Hippocampal place coding during dentate spikes aligns to the mouse’s current spatial location, unlike the memory replay accompanying sharp-wave ripples. Furthermore, inhibiting neural activity during dentate spikes disrupts associative memory formation. Thus, dentate spikes represent a distinct brain state and support memory during non-locomotor behaviour, extending the repertoire of cognitive processes beyond the classical offline functions.

Impact of IoT-Based Environmental Monitoring on Lab Safety and Sustainability

Several internal and external dangers might threaten a laboratory, the institution, and the public if not addressed properly. These hazards are addressed by our extensive laboratory monitoring system. This device detects elevated temperatures, gas leaks, fires, and solution pH. Elements of this system include an Esp32 microcontroller, LCD, Arduino Uno, mq2 gas sensor, DS18B20 temperature sensor, flame sensor, relay, water pump, and pH sensor for acidity measurement. The Arduino IDE controls sensors. Once the temperature reaches 50 degrees Celsius, an alarm, red LED, and mobile phone notification activate. Gas leaks activate a green LED, an alarm, and a message. Flame sensors notify and start water pumps when fires occur. Gas leaks and fires activate a buzzer. The IoT offers essential incident reporting and remote laboratory monitoring. The code is written in Arduino C++.

High-temperature axial tensile property and fire resisting performance of CFRP strand cable

High-temperature tensile tests and fire resisting performance tests were conducted on carbon fiber reinforced polymer (CFRP) strand cable, respectively, to identify axial tensile property deterioration of CFRP strand tendon (i.e., cable without initial tensile load) under 100–600℃ temperature range and determine fire resisting duration and ultimate temperature of CFRP strand cable with initial tensile load ratio from 0.2 to 0.8. High-temperature axial tensile property and fire resisting performance of different cables including CFRP and steel cables were compared to identify influence of non-uniform load distribution. The obtained results demonstrated that the dominate failure modes of specimen in both high-temperature tensile test and fire resisting performance test are tensile failure. Due to the degradation of mechanical property of resin matrix and bonding performance for resin matrix-fiber bundle interface exposed to elevated temperature, axial tensile strength of CFRP strand tendon degraded by 33.4% and 80.8% under 210℃ (glass transition temperature) and 600℃, respectively, compared to that under ambient temperature. Fire resisting duration of CFRP strand cables varied from 1.3 to 16.4 mins, indicating poor fire resisting performance. Reduction coefficient of bearing capacity for CFRP strand tendon decreased from 0.96 to 0.74 as temperature varied from 25 to 400℃, and then increased to 1.54 at 600℃. Compared to ribbed CFRP cable, CFRP strand cables with initial tensile load ratios ranging of 0.4 ∼ 0.8 (low ultimate temperatures) display worse fire resisting performance due to the prominent non-uniform load distribution among seven wires. Axial tensile strength and reduction coefficient of bearing capacity for CFRP strand tendon exposed to elevated temperature and fire resisting duration of CFRP strand cable and ribbed CFRP cable can be accurately predicted by the developed practical models.

War drives forest fire risks and highlights the need for more ecologically-sound forest management in post-war Ukraine.

Since 24 February 2022, Ukraine has experienced full-scale military aggression initiated by the Russian Federation. The war has had a major negative impact on vegetation cover of war-affected regions. We explored interactions between pre-war forest management and the impacts of military activities in three of the most forested Ukrainian areas of interest (AOI), affected by the war. These were forests lying between Kharkiv and Luhansk cities (AOI 'East'), forests along the Dnipro River delta (AOI 'Kherson'), and those of the Chornobyl Exclusion Zone (AOI CEZ). We used Sentinel satellite imagery to create damaged forest cover masks for the year 2022. We mapped forests with elevated fire hazard, which was defined as a degree of exposure to the fire-supporting land use (mostly an agricultural land, a common source of ignitions in Ukraine). We evaluated the forest disturbance rate in 2022, as compared to pre-war rates. We documented significant increases in non-stand replacing disturbances (low severity fires and non-fire disturbances) for all three of the AOIs. Damaged forest cover varied among the AOIs (24,180 ± 4,715ha, or 9.3% ± 1.8% in the 'East' AOI; 7,293 ± 1,925ha, or 15.7% ± 4.1% in the 'Kherson' AOI; 7,116 ± 1,274ha, or 5.0% ± 0.9% in the CEZ AOI). Among the forests damaged in 2022, the 'Kherson' AOI will likely have the highest proportion of an area with elevated fire hazard in the coming decades, as compared to other regions (89% vs. 70% in the 'East' and CEZ AOIs respectively). Future fire risks and extensive war-related disturbance of forest cover call for forest management to develop strategies explicitly addressing these factors.

Experimental and numerical study of an elevated pool fire scenario in a confined and mechanically ventilated compartment

The present work deals with an experimental and numerical investigation of an elevated pool fire scenario in a confined and forced ventilated compartment. Although often encountered in industrial installations or in common buildings, this type of configuration is rarely studied in the literature. This study is supported by a set of two large-scale fire experiments performed in the framework of the OECD-PRISME3 project and numerical simulations (RANS and LES methods) carried out with the CALIF3S-Isis software. The objective is to improve the physical understanding of the phenomena that are experimentally highlighted and to assess the capabilities of Computational Fluid Dynamics (CFD) on this type of configuration. First, the comparison between the two large-scale fire tests (one elevated and its equivalent on the ground) exhibits a strong modification of the fuel mass loss rate associated with a change in the thermal and species stratifications. Then, a preliminary simulation using a predictive approach commonly used and efficient for the case of a ground fire scenario shows by contrast its limitations when applied to the case of the elevated fire. Therefore, in addition to the essential step consisting in the validation of the code with a prescribed approach on this type of elevated fire, the simulations also reveal a specific phenomenology (smoke filling, strong vitiation, oxygen-pumping, …). Finally, taking into account these particularities allows in fine, for the studied case, the improvement of the prediction of the mass loss rate of the fire.

A Link Between Hydroclimate Variability and Biomass Burning During the Last Millennium in the Interior Pacific Northwest

AbstractWe present oxygen isotope and charcoal accumulation records from two lakes in eastern Washington that have sufficient temporal resolution to quantitatively compare with tree‐ring records and meteorological data. Hydroclimate reconstructions from tree‐rings and lake sediments show close correspondence after accounting for seasonal‐ to centennial‐ scale temporal sensitivities. Carbonate δ18O measurements from Castor and Round lakes reveal that the Medieval Climate Anomaly (MCA) experienced wetter November‐March conditions than the Little Ice Age (LIA). Charcoal records from Castor, Round, and nearby lakes show elevated fire activity during the LIA compared to the MCA. Increased multidecadal hydroclimate variability after 1250 CE is evident in proxy records throughout western North America. In the Upper Columbia River Basin, multidecadal wet periods during the LIA may have enhanced fuel loads that burned in subsequent dry periods. A notable decline in biomass burning occurred with Euro‐American settlement in the late nineteenth century.

Acetyl Transferase EP300 Deficiency Leads to Chronic Replication Stress in Adult T-Cell Leukemia/Lymphoma

Mutations in the epigenetic regulator and global transcriptional activator, E1A binding protein (EP300), is being increasingly reported in aggressive hematological malignancies including adult T-cell leukemia/lymphoma (ATLL). However, the mechanistic contribution of EP300 dysregulation to cancer initiation and progression are currently unknown. Independent inhibition of EP300 in human cells results in the differential expression of genes involved in regulating the cell cycle, DNA replication and DNA damage response. Nevertheless, specific function played by EP300 in DNA replication initiation, progression and replication fork integrity has not been studied. Here, using ATLL cells as a disease model to study EP300 deficiency and an EP300-selective PROTAC degrader, as a pharmacologic tool, we reveal that EP300-mutated cells display prolonged cell cycle kinetics, due to pronounced dysregulations in DNA replication dynamics leading to persistent genomic instability. Aberrant DNA replication in EP300-mutated cells is characterized by elevated replication origin firing due to increased replisome pausing genome-wide. We demonstrate that EP300 deficiency results in nucleolytic degradation of nascently synthesized DNA at stalled forks due to a prominent defect in fork stabilization and protection. This in turn results in the accumulation of single stranded DNA gaps at collapsed replication forks, in EP300-deficient cells. Inhibition of Mre11 nuclease rescues the ssDNA accumulation indicating a dysregulation in downstream mechanisms that restrain nuclease activity at stalled forks. Importantly, we find that the absence of EP300 results in decreased expression of BRCA2 protein expression and a dependency on POLD3-mediated error-prone replication restart mechanisms. The overall S-phase abnormalities observed lead to under-replicated DNA in G2/M that instigates mitotic DNA synthesis. This in turn is associated with mitotic segregation defects characterized by elevated micronuclei formation, transmission of unrepaired inherited DNA lesions in the subsequent G1-phase and accumulation of cytosolic DNA in EP300-deficient cells. However, EP300 deficient cells show a significant defect in innate immune system activation. Altogether these results suggest that mutations in EP300 cause chronic DNA replication stress, persistent genomic instability and innate immune system evasion underlie aggressive chemo-resistant tumorigenesis in humans.

Mega-scale movie-fields in the mouse visuo-hippocampal network.

Natural visual experience involves a continuous series of related images while the subject is immobile. How does the cortico-hippocampal circuit process a visual episode? The hippocampus is crucial for episodic memory, but most rodent single unit studies require spatial exploration or active engagement. Hence, we investigated neural responses to a silent movie (Allen Brain Observatory) in head-fixed mice without any task or locomotion demands, or rewards. Surprisingly, a third (33%, 3379/10263) of hippocampal -dentate gyrus, CA3, CA1 and subiculum- neurons showed movie-selectivity, with elevated firing in specific movie sub-segments, termed movie-fields, similar to the vast majority of thalamo-cortical (LGN, V1, AM-PM) neurons (97%, 6554/6785). Movie-tuning remained intact in immobile or spontaneously running mice. Visual neurons had >5 movie-fields per cell, but only ~2 in hippocampus. The movie-field durations in all brain regions spanned an unprecedented 1000-fold range: from 0.02s to 20s, termed mega-scale coding. Yet, the total duration of all the movie-fields of a cell was comparable across neurons and brain regions. The hippocampal responses thus showed greater continuous-sequence encoding than visual areas, as evidenced by fewer and broader movie-fields than in visual areas. Consistently, repeated presentation of the movie images in a fixed, but scrambled sequence virtually abolished hippocampal but not visual-cortical selectivity. The preference for continuous, compared to scrambled sequence was eight-fold greater in hippocampal than visual areas, further supporting episodic-sequence encoding. Movies could thus provide a unified way to probe neural mechanisms of episodic information processing and memory, even in immobile subjects, across brain regions, and species.

Mega-scale movie-fields in the mouse visuo-hippocampal network

Natural visual experience involves a continuous series of related images while the subject is immobile. How does the cortico-hippocampal circuit process a visual episode? The hippocampus is crucial for episodic memory, but most rodent single unit studies require spatial exploration or active engagement. Hence, we investigated neural responses to a silent movie (Allen Brain Observatory) in head-fixed mice without any task or locomotion demands, or rewards. Surprisingly, a third (33%, 3379/10263) of hippocampal –dentate gyrus, CA3, CA1 and subiculum– neurons showed movie-selectivity, with elevated firing in specific movie sub-segments, termed movie-fields, similar to the vast majority of thalamo-cortical (LGN, V1, AM-PM) neurons (97%, 6554/6785). Movie-tuning remained intact in immobile or spontaneously running mice. Visual neurons had >5 movie-fields per cell, but only ~2 in hippocampus. The movie-field durations in all brain regions spanned an unprecedented 1000-fold range: from 0.02s to 20s, termed mega-scale coding. Yet, the total duration of all the movie-fields of a cell was comparable across neurons and brain regions. The hippocampal responses thus showed greater continuous-sequence encoding than visual areas, as evidenced by fewer and broader movie-fields than in visual areas. Consistently, repeated presentation of the movie images in a fixed, but scrambled sequence virtually abolished hippocampal but not visual-cortical selectivity. The preference for continuous, compared to scrambled sequence was eight-fold greater in hippocampal than visual areas, further supporting episodic-sequence encoding. Movies could thus provide a unified way to probe neural mechanisms of episodic information processing and memory, even in immobile subjects, across brain regions, and species.

A Pathogenic Missense Mutation in Kainate Receptors Elevates Dendritic Excitability and Synaptic Integration through Dysregulation of SK Channels.

Numerous rare variants that cause neurodevelopmental disorders (NDDs) occur within genes encoding synaptic proteins, including ionotropic glutamate receptors. However, in many cases, it remains unclear how damaging missense variants affect brain function. We determined the physiological consequences of an NDD causing missense mutation in the GRIK2 kainate receptor (KAR) gene, that results in a single amino acid change p.Ala657Thr in the GluK2 receptor subunit. We engineered this mutation in the mouse Grik2 gene, yielding a GluK2(A657T) mouse, and studied mice of both sexes to determine how hippocampal neuronal function is disrupted. Synaptic KAR currents in hippocampal CA3 pyramidal neurons from heterozygous A657T mice exhibited slow decay kinetics, consistent with incorporation of the mutant subunit into functional receptors. Unexpectedly, CA3 neurons demonstrated elevated action potential spiking because of downregulation of the small-conductance Ca2+ activated K+ channel (SK), which mediates the post-spike afterhyperpolarization. The reduction in SK activity resulted in increased CA3 dendritic excitability, increased EPSP-spike coupling, and lowered the threshold for the induction of LTP of the associational-commissural synapses in CA3 neurons. Pharmacological inhibition of SK channels in WT mice increased dendritic excitability and EPSP-spike coupling, mimicking the phenotype in A657T mice and suggesting a causative role for attenuated SK activity in aberrant excitability observed in the mutant mice. These findings demonstrate that a disease-associated missense mutation in GRIK2 leads to altered signaling through neuronal KARs, pleiotropic effects on neuronal and dendritic excitability, and implicate these processes in neuropathology in patients with genetic NDDs.SIGNIFICANCE STATEMENT Damaging mutations in genes encoding synaptic proteins have been identified in various neurodevelopmental disorders, but the functional consequences at the cellular and circuit level remain elusive. By generating a novel knock-in mutant mouse, this study examined the role of a pathogenic mutation in the GluK2 kainate receptor (KAR) subunit, a subclass of ionotropic glutamate receptors. Analyses of hippocampal CA3 pyramidal neurons determined elevated action potential firing because of an increase in dendritic excitability. Increased dendritic excitability was attributable to reduced activity of a Ca2+ activated K+ channel. These results indicate that a pathogenic KAR mutation results in dysregulation of dendritic K+ channels, which leads to an increase in synaptic integration and backpropagation of action potentials into distal dendrites.

Burning rate of elevated pool fire in a well-ventilated compartment: Effects of radiative heat fluxes

Elevated pool fires are potentially exposed to the feedback of radiative heat fluxes from the ceiling that can modify the mass loss rate. In this regard, an experimental study was carried-out in a reduced-scale enclosure with a pool fire brought increasingly closer to the ceiling of the compartment. The objective is to study the effect on the mass loss rate of the increase in radiative heat fluxes without any air vitiation effect. The device is equipped with a mechanical ventilation system to allow the flame to develop in a well-oxygenated environment. The fire sources used are circular pans with diameters between 0.09 and 0.175 m, filled with dodecane. Results show that, as long as the flame does not impinge on the ceiling, the mass loss rate remains quasi-constant. On the other hand, when the flame impinges on the ceiling, the mass loss rate increases drastically and can be multiplied by a factor 2–3 compared to the reference value when the pool fire is located on the ground. Scaling parameters, showing the generic aspect of the results, are finally proposed considering a dimensionless elevation h*. It allows to gather all experimental data on the same curve for all the fire sources tested.

Effect of variegated biosolids incorporation on the technological properties of fired clay bricks using Taguchi method

Green routes to effectively mitigate the extensive generation of variegated biosolids (VB) from the artisanal basketry sector has been specially constrained with traditional waste management practices. In this investigation, VB is used as a pore forming material in the development of fired clay bricks. Three compositional different bricks formulated with different dosages of VB (i.e., 0, 6 and 12 wt%) inclusion in brickmaking clay (BC) were fired at 900, 1000 and 1100 °C temperatures, and assessed for their physico-mechanical and thermal properties. Weight loss (WL) results showed the bricks WL increased with elevated firing and high addition VB admixed proportion. The highest 12.8% WL was observed among the BS12–1100 bricks. Fired shrinkage (FS) values were within recommended limits of 2.4–7.6%. Apparent Porosity (AP) results ranged from 19.3% to 38.6%. AP increased by 52.3% with VB addition but decreased up to 23.83% due to improved firing. Water absorption (WA) results were mostly found within the quality standards of 9.1 – 19.8%. Bulk density (BD) variations were observed between 1.3 g/cm3 and 2.2 g/cm3. Compressive strength (CS) reductions were in the acceptable range of 25.0 – 9.1 MPa. The thermal conductivity (TC) test results of the bricks showed a 28.59% improvement in the thermal insulation properties of the bricks. The Taguchi method revealed BS12–900 brick series as best optimized products due to its acceptable 9.1 MPa CS and least TC (0.452 W/mK). Thus, the usage of VB for brick production has an important contributory role to the economy and ecology of Ghana.

Thermal resistance of high strength PVA fiber reinforced engineered cementitious composites containing basalt fiber

Engineered cementitious composites (ECC) predominantly prefer polyvinyl alcohol (PVA) fiber as reinforcement. However, PVA fiber experiences melting at approximately 235 °C. When structures with high strength ECC (HSECC) occasionally suffer elevated temperatures or fire, PVA fiber would inevitably induce deterioration in mechanical properties and increase the probability of structural failure. In present study, basalt fiber with high temperature resistance was selected to replace PVA fiber, visual observations and strength deterioration of HSECC were evaluated after heating. The incorporation of basalt fiber has shown potential ability in improving flexural behavior of HSECC upon elevated temperatures. Interfacial transition zone (ITZ) is observed to be effectively enhanced under 200 and 400℃.