Increase In Firing Frequency Research Articles

Wildfire effects on soil bacterial community and its potential functions in a permafrost region of Canada

Boreal forests in permafrost zone store significant quantities of carbon that are readily threatened by increases in fire frequency and temperature due to climate change. Soil carbon is primarily released by microbial decomposition that is sensitive to environmental conditions. Under increasing disturbances of wildfire, there is a pressing need to understand interactions between wildfires and microbial communities, thereby to predict soil carbon dynamics. Using Illumina MiSeq sequencing of bacterial 16S rDNA and GeoChip 5.0K, we compared bacterial communities and their potential functions at surface and near-surface permafrost layers across a chronosequence (>100 years) of burned forests in a continuous permafrost zone. Postfire soils in the Yukon and the Northwest Territories, Canada, showed a marked increase in active layer thickness. Our results showed that soil bacterial community compositions and potential functions altered in 3-year postfire forest (Fire3) comparing to the unburned forests. The relative abundance of Ktedonobacteria (Chloroflexi) was higher in Fire3 surface soils, while Alphaproteobacteria and Betaproteobacteria (Proteobacteria) were more abundant in unburned ones. Approximately 37% of the variation in community composition can be explained by abiotic variables, whereas only 2% by biotic variables. Potential functional genes, particularly for carbon degradation and anammox, appeared more frequent in Fire3 than in unburned soils. Variations in functional gene pools were mainly driven by environmental factors (39%) and bacterial communities (20%; at phylum level). Unexpectedly, wildfire solely altered bacterial communities and their functional potentials of the surface layers, not the near-permafrost layers. Overall, the response of bacterial community compositions and functions to wildfire and the environment provides insights to re-evaluate the role of bacteria in decomposition.

Modulation of Kv3.1/Kv3.2 promotes gamma oscillations by rescuing Aβ-induced desynchronization of fast-spiking interneuron firing in an AD mouse model in vitro.

Gamma oscillations (30-80Hz) are important for cognitive functions and depend on the synchronized activity of fast-spiking interneurons (FSN), which is crucial for network stability. Gamma oscillations are degraded in Alzheimer's disease (AD) patients exhibiting cognitive impairment, with the degree of cognitive decline correlating with the severity of gamma disruption in response to neurotoxic amyloid-beta peptide (Aβ). Small molecule compounds EX15 and RE01modulate Kv3.1/Kv3.2 potassium channels on FSN, resulting in faster activation kinetics and increased firing frequency, suggesting direct consequences for cognition-relevant gamma oscillations, particularly in a situation where network activity is pathologically compromised in the presence of neurotoxic Aβ. Using electrophysiological techniques in an in vitro AD model, we found a significant effect of EX15 and RE01 with respect to counteracting toxic Aβ effects on neuronal dynamics, advocating for targeting FSN activity to rescue cognitive performance from impairment caused by neurodegenerative triggers. Rhythmic electrical activity in neuronal networks such as gamma oscillations (30-80Hz) underlies cognitive functions such as sensory perception, attention and memory. Gamma oscillations are disrupted in Alzheimer's disease (AD) patients and animal AD models, with the severity of cognitive decline correlating with the degree of rhythm disruption. Misfolded amyloid-β peptide (Aβ) is assumed to be a key trigger of AD pathology and has been show to de-synchronize action potential firing in fast-spiking interneurons (FSN), which is crucial for entraining neuronal network activity into the gamma rhythm. The synchronizing activity of FSN therefore has become one of the most suitable targets to counteract disease-driven degradation of gamma oscillations and consequent cognitive decline. EX15 and RE01 are small-molecule compounds that modulate Kv3.1/Kv3.2 potassium channels, resulting in faster activation kinetics and increased FSN firing frequency. In the present study, we investigated the potential pro-cognitive effects of EX15 and RE01 by testing their ability to modulate FSN activity during ongoing gamma oscillations in normal and Aβ-disrupted network states in mouse hippocampus in vitro. In the compromised, but not the uncompromised, network state with gamma oscillations partially disrupted by Aβ, both compounds improve gamma oscillation regularity by promoting re-synchronization of FSN action potential firing. Our data suggest a therapeutic potential for compounds such as EX15 and RE01, which can rescue normal action potential firing parameters in FSN, in the search for disease-modifying drug candidates counteracting the progressive dysfunction of neuronal network dynamics that underlies the cognitive impairment typical of AD and other cognitive brain disorders.

Mapping of the FGF14:Nav1.6 complex interface reveals FLPK as a functionally active peptide modulating excitability.

The voltage‐gated sodium (Nav) channel complex is comprised of pore‐forming α subunits (Nav1.1–1.9) and accessory regulatory proteins such as the intracellular fibroblast growth factor 14 (FGF14). The cytosolic Nav1.6 C‐terminal tail binds directly to FGF14 and this interaction modifies Nav1.6‐mediated currents with effects on intrinsic excitability in the brain. Previous studies have identified the FGF14V160 residue within the FGF14 core domain as a hotspot for the FGF14:Nav1.6 complex formation. Here, we used three short amino acid peptides around FGF14V160 to probe for the FGF14 interaction with the Nav1.6 C‐terminal tail and to evaluate the activity of the peptide on Nav1.6‐mediated currents. In silico docking predicts FLPK to bind to FGF14V160 with the expectation of interfering with the FGF14:Nav1.6 complex formation, a phenotype that was confirmed by the split‐luciferase assay (LCA) and surface plasmon resonance (SPR), respectively. Whole‐cell patch‐clamp electrophysiology studies demonstrate that FLPK is able to prevent previously reported FGF14‐dependent phenotypes of Nav1.6 currents, but that its activity requires the FGF14 N‐terminal tail, a domain that has been shown to contribute to Nav1.6 inactivation independently from the FGF14 core domain. In medium spiny neurons in the nucleus accumbens, where both FGF14 and Nav1.6 are abundantly expressed, FLPK significantly increased firing frequency by a mechanism consistent with the ability of the tetrapeptide to interfere with Nav1.6 inactivation and potentiate persistent Na+ currents. Taken together, these results indicate that FLPK might serve as a probe for characterizing molecular determinants of neuronal excitability and a peptide scaffold to develop allosteric modulators of Nav channels.

Repeated fire altered succession and increased fire behavior in basin big sagebrush–native perennial grasslands

AbstractThe structure and composition of sagebrush‐dominated ecosystems have been altered by changes in fire regimes, land use, invasive species, and climate change. This often decreases resilience to disturbance and degrades critical habitat for species of conservation concern. Basin big sagebrush (Artemisia tridentata ssp. tridentata) ecosystems, in particular, are greatly reduced in distribution as land has been converted to agriculture and other land uses. The fire regime, relative proportions of shrub and grassland patches, and the effects of repeated burns in this ecosystem are poorly understood. We quantified postfire patterns of vegetation accumulation and modeled potential fire behavior on sites that were burned and first measured in the late 1980s at John Day Fossil Beds National Monument, Oregon, USA. The area partially reburned 11 yr after the initial fire, allowing a comparison of one vs. two fires. Repeated burns shifted composition from shrub‐dominated to prolonged native herbaceous dominance. Fifteen years following one fire, the native‐dominated herbaceous component was 44% and live shrubs were 39% of total aboveground biomass. Aboveground biomass of twice‐burned sites (2xB; burned 26 and 15 yr prior) was 71% herbaceous and 12% shrub. Twenty‐six years after fire, total aboveground biomass was 113–209% of preburn levels, suggesting a fire‐return interval of 15–25 yr. Frequency and density of Pseudoroegneria spicata and Festuca idahoensis were not modified by fire history, but Poa secunda was reduced by repeated fire, occurring in 84% of plots burned 26 yr prior, 72% of plots burned 15 yr prior, and 49% in 2xB plots. Nonnative annual Bromus tectorum occurred at a frequency of 74%, but at low density with no differences due to fire history. Altered vegetation structure modified fire behavior, with modeled rates of fire spread in 2xB sites double that of once‐burned sites. This suggests that these systems likely were historically composed of a mosaic of shrub and grassland. However, contemporary increases in fire frequency will likely create positive feedbacks of more intense fire behavior and prolonged periods of early‐successional vegetation in basin big sagebrush communities.

Simulated Increases in Fire Activity Reinforce Shrub Conversion in a Southwestern US Forest

Fire exclusion in historically frequent-fire forests of the southwestern United States has altered forest structure and increased the probability of high-severity fire. Warmer and drier conditions, coupled with dispersal distance limitations, are impeding tree seedling establishment and survival following high-severity fire. High-severity patches are commonly dominated by non-forest vegetation, a state that can be reinforced by subsequent fire events. We sought to determine the influence of fire probability on post-fire vegetation development in a severely burned landscape in New Mexico, USA. We used LANDIS-II to simulate three fire probability scenarios—historical fire probability, contemporary fire probability, and the mean of the two—with contemporary climate. As fire probability increased, the mean size of the largest fires and the mean landscape fire severity increased. These changes in fire characteristics resulted in decreased total aboveground biomass and photosynthetic capacity on the landscape after 50 years. Additionally, the distribution of individual species biomass shifted, with early successional species, especially those that resprout after fire, increasing as a fraction of total biomass with increasing fire occurrence. Counter to empirical data, our simulations did not show a conifer establishment limitation, suggesting a source of uncertainty that will need to be addressed to improve projections of forest dynamics under future climate. Even without limited conifer regeneration, continued increases in fire frequency are likely to favor resprouting species and result in a loss of forest biomass and ecosystem productivity in this southwestern forest landscape.

Bifurcations of Negative Responses to Positive Feedback Current Mediated by Memristor in a Neuron Model with Bursting Patterns

In contrast to traditional viewpoint that positive feedback current always enhances neural firing activities, in the present paper, we identify that the excitatory feedback current mediated by memristor can induce negative responses of bursting patterns, which can be well interpreted with bifurcations. For the Hindmarsh–Rose neuron model without memristor, the period-adding bifurcations of bursting patterns and increase of firing frequency can be induced by increasing the excitatory effect of the background current. After introducing a memristor to simulate the biological synapse or electromagnetic induction effect, inverse period-adding or complex bifurcations of bursting patterns are induced by the excitatory feedback current mediated by the memristor. The number of spikes per burst becomes smaller and the firing frequency becomes lower when increasing the positive feedback gain. Such negative responses of bursting patterns to the positive feedback current are demonstrated in a circuit designed with Digital Signal Processor systems of the MatLab software. Furthermore, the underlying bifurcation mechanism of the negative responses to the positive feedback is acquired with fast–slow variable dissection method. With increasing feedback gain, the initial phase of the burst, which corresponds to a saddle-node bifurcation point of the fast subsystem, delays, while the termination phase of the burst, which corresponds to a saddle-homoclinic bifurcation point, remains unchanged. Therefore, the burst becomes narrower with increasing feedback gain, which leads to decrease in the number of spikes within a burst and decrease in firing frequency. The results present a paradoxical nonlinear phenomenon and the dynamical mechanism, which is helpful for understanding the functions of memristor and roles of the electromagnetic induction current.

Long-Term Fire Regime Modifies Carbon and Nutrient Dynamics in Decomposing Eucalyptus pilularis Leaf Litter

The changes in fire regimes expected under climate change are likely to disrupt the biogeochemical cycling of carbon (C) and nutrients in forest ecosystems. Plant litter decomposition is a critical step in the terrestrial biogeochemical cycle, and is an important determinant of fire fuel load and forest C balance. We conducted a 277-day leaf litter decomposition experiment in an Australian eucalypt forest to test whether three contrasting, long-term fire regimes (no burning [NB], 4-yearly burning, and 2-yearly burning) were associated with different C and nutrient dynamics during litter decomposition. Fire regime had strong effects on many litter properties, including overall rates of decomposition and C loss, which were greatest in the NB treatment, suggesting that fire regime can modify the rate at which C is returned from litter to soil or the atmosphere. This has potentially important implications for soil C storage and atmospheric CO2 concentrations under a changing climate. High-frequency fire was associated with litter nutrient depletion and high microbial nutrient demand, but did not affect nutrient loss rates from decomposing litter, suggesting conservative use and retention of nutrients by the litter microbial biomass. These effects differed qualitatively between 2- and 4-yearly burning regimes, and they show how decadal-scale increases in fire frequency might contribute to soil nutrient depletion by disrupting decomposition. Many effects of fire regime on litter properties throughout decomposition were sensitive to litter bag re-collection date, suggesting that seasonal factors moderate the effects of fire regime, and that the role of fire regime-altered litter chemistry in shaping decomposition may be secondary to that of fire regime-altered environmental variables. Together, our findings highlight the potential consequences of long-term increases in prescribed fire frequency for litter decomposition and the storage and cycling of C and nutrients in eucalypt forests, and reveal the specific importance of average burn frequency in this context.

Hyperexcitability of VTA dopaminergic neurons in male offspring exposed to physical or psychological prenatal stress

Prenatal stress (PS) exposure leads to cognitive and behavioral alterations in offspring including an increased risk of substance abuse and anxiety disorders. Signalling from dopamine (DA) neurons of the ventral tegmental area (VTA) in the mesoaccumbal and mesocortical pathways plays a vital role in drug dependency and anxiety behavior. To provide further knowledge about the changes in drug seeking behavior and anxiety behaviors in prenatally stressed mice, we conducted ex vivo investigations in VTA brain slices of adult male PS offspring to evaluate the effects of two types of PS (physical vs. psychological) on activity of DA neurons. Elevated plus maze (EPM) was used to assess anxiety-like behaviors and conditioned place preference (CPP) was used to evaluate drug reinforcing effects in mice. An increased anxiety-like behavior and preference to morphine was observed in prenatally stressed mice. PS VTA DA cells exhibited greater Ih current and a higher frequency and amplitude of sEPSCs, which were consistent with a greater degree of pre- or postsynaptic excitability of the VTA. This was confirmed by lower rheobase and lower firing thresholds in PS VTA neurons, as well as increases in spontaneous firing frequency. When taken together, these data suggest that alterations in VTA DA neurons in this mouse model of prenatal stress might be associated with later life alterations in drug seeking and anxiety-like behaviors through their role in mesocortical and mesoaccumbal pathways.

Will Lynx Lose Their Edge? Canada Lynx Occupancy in Washington

ABSTRACTPopulations of species located at southern range edges may be particularly vulnerable to the effects of climate change as warming temperatures and subsequent changes to ecosystems exceed species‐specific tolerances. One such species is Canada lynx (Lynx canadensis), a cold‐adapted mesocarnivore that maintains a large core population in Alaska, USA, and Canada but exists within several peripheral populations in the contiguous United States. Increases in temperature, declines in snow pack, and climate‐influenced increases in fire frequency and intensity, could negatively affect lynx populations, threatening their long‐term persistence in the continental United States. Despite these threats, our understanding of broad‐scale effects on lynx occupancy and the extent of current lynx distribution in many of these peripheral populations is minimal. We conducted an occupancy survey of lynx in Washington, USA, using a spatially extensive camera‐trapping array covering 7,000 km2 of potential lynx habitat. We used the resulting database of detection data to develop single‐season occupancy models to examine the abiotic and biotic effects on current lynx occupancy and predict future lynx distribution based on climate change forecasts. Our results show lynx occupancy across the Washington landscape is restricted and dictated largely by abiotic factors, disturbance regimes, and distance from source populations in Canada. Predictions of future distribution suggest lynx will be increasingly challenged by climatic changes, particularly at the southern and lower elevation portions of their range in Washington. Our results paint an alarming picture for lynx persistence in Washington that is relevant to current deliberations regarding lynx delisting from the Endangered Species Act. Our simple camera design was a highly effective method for surveying lynx across broad spatial scales, and could be a key monitoring tool for lynx that is easy to implement by researchers and government agencies. © 2020 The Wildlife Society.

Post-Fire Resprouting in New Zealand Woody Vegetation: Implications for Restoration

Resprouting is an important trait that allows plants to persist after fire and is considered a key functional trait in woody plants. While resprouting is well documented in fire-prone biomes, information is scarce in non-fire-prone ecosystems, such as New Zealand (NZ) forests. Our objective was to investigate patterns of post-fire resprouting in NZ by identifying the ability of species to resprout and quantifying the resprouting rates within the local plant community. Fire occurrence is likely to increase in NZ as a consequence of climate change, and this investigation addresses an important knowledge gap needed for planning restoration actions in fire-susceptible regions. The study was conducted in two phases: (1) A detailed review of the resprouting ability of the NZ woody flora, and (2) a field study where the post-fire responses of plants were quantified. The field study was undertaken in the eastern South Island, where woody plants (>5 cm diameter at 30 cm height) were sampled in 10 plots (10x10 m), five- and 10-months post-fire. The research synthesized the resprouting ability of 73 woody species and is the first to provide extensive quantitative data on resprouting in NZ. Most of the canopy dominant species were non-resprouters, but many smaller trees and shrubs were capable of resprouting, despite their evolution in an environment with low fire frequency. Species composition and abundance were important predictors of resprouting patterns among plots, with similar communities resulting in similar resprouting responses. Resprouting capacity provides species with a competitive advantage in the post-fire recovery. We suggest that it is possible to engineer more fire resilient restoration plantings by planting higher proportions of the resprouters identified in this study. The incorporation of resprouting as a trait in restoration plans is likely to be relevant not just in NZ, but also in other non-fire-prone regions facing increases in fire frequency.

Response to fire by a forest specialist in isolated montane forest

Fire events have increased in scale and severity due to hotter, drier conditions brought on by climate change and fire suppression. Extreme fire events can be detrimental to forest specialists, especially populations at the edge of the species range, where conditions can vary from those within the core of the range. The San Bernardino flying squirrel (Glaucomys oregonensis californicus) is the southernmost subspecies of Humboldt’s flying squirrel and occurs only in the San Bernardino Mountains of southern California after apparent extirpation from the nearby San Jacinto Mountains. We used non-invasive methods to assess how fire affects flying squirrel occupancy. We surveyed for flying squirrels in burned and unburned areas of the San Bernardino Mountains, and measured habitat features to construct occupancy models. Our top models indicated that flying squirrels occupy lower burn severities but could still occur at higher burn severities if canopy cover remained intact, forest duff remained deep, and tree mortality remained low, especially on steeper slopes. Our study illustrates the ability of San Bernardino flying squirrels, and the potential for other flying squirrels, to survive major fire events and maintain their role in the forest ecosystem. Such results are especially important for species management and understanding how parts of an ecosystem can react as fire frequency and severity increases.

Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.

The dentate gyrus (DG) in the hippocampus may play key roles in remembering distinct episodes through pattern separation, which may be subserved by the sparse firing properties of granule cells (GCs) in the DG. Low intrinsic excitability is characteristic of mature GCs, but ion channel mechanisms are not fully understood. Here, we investigated ionic channel mechanisms for firing frequency regulation in hippocampal GCs using male and female mice, and identified Kv4.1 as a key player. Immunofluorescence analysis showed that Kv4.1 was preferentially expressed in the DG, and its expression level determined by Western blot analysis was higher at 8-week than 3-week-old mice, suggesting a developmental regulation of Kv4.1 expression. With respect to firing frequency, GCs are categorized into two distinctive groups: low-frequency (LF) and high-frequency (HF) firing GCs. Input resistance (Rin) of most LF-GCs is lower than 200 MΩ, suggesting that LF-GCs are fully mature GCs. Kv4.1 channel inhibition by intracellular perfusion of Kv4.1 antibody increased firing rates and gain of the input-output relationship selectively in LF-GCs with no significant effect on resting membrane potential and Rin, but had no effect in HF-GCs. Importantly, mature GCs from mice depleted of Kv4.1 transcripts in the DG showed increased firing frequency, and these mice showed an impairment in contextual discrimination task. Our findings suggest that Kv4.1 expression occurring at late stage of GC maturation is essential for low excitability of DG networks and thereby contributes to pattern separation.SIGNIFICANCE STATEMENT The sparse activity of dentate granule cells (GCs), which is essential for pattern separation, is supported by high inhibitory inputs and low intrinsic excitability of GCs. Low excitability of GCs is thought to be attributable to a high K+ conductance at resting membrane potentials, but this study identifies Kv4.1, a depolarization-activated K+ channel, as a key ion channel that regulates firing of GCs without affecting resting membrane potentials. Kv4.1 expression is developmentally regulated and Kv4.1 currents are detected only in mature GCs that show low-frequency firing, but not in less mature high-frequency firing GCs. Furthermore, mice depleted of Kv4.1 transcripts in the dentate gyrus show impaired pattern separation, suggesting that Kv4.1 is crucial for sparse coding and pattern separation.

Modeling the Effect of Temperature on Membrane Response of Light Stimulation in Optogenetically-Targeted Neurons.

Optogenetics is revolutionizing Neuroscience, but an often neglected effect of light stimulation of the brain is the generation of heat. In extreme cases, light-generated heat kills neurons, but mild temperature changes alter neuronal function. To date, most in vivo experiments rely on light stimulation of neural tissue using fiber-coupled lasers of various wavelengths. Brain tissue is irradiated with high light power that can be deleterious to neuronal function. Furthermore, absorbed light generates heat that can lead to permanent tissue damage and affect neuronal excitability. Thus, light alone can generate effects in neuronal function that are unrelated to the genuine “optogenetic effect.” In this work, we perform a theoretical analysis to investigate the effects of heat transfer in rodent brain tissue for standard optogenetic protocols. More precisely, we first use the Kubelka-Munk model for light propagation in brain tissue to observe the absorption phenomenon. Then, we model the optothermal effect considering the common laser wavelengths (473 and 593 nm) used in optogenetic experiments approaching the time/space numerical solution of Pennes' bio-heat equation with the Finite Element Method. Finally, we then modeled channelrhodopsin-2 in a single and spontaneous-firing neuron to explore the effect of heat in light stimulated neurons. We found that, at commonly used light intensities, laser radiation considerably increases the temperature in the surrounding tissue. This effect alters action potential size and shape and causes an increase in spontaneous firing frequency in a neuron model. However, the shortening of activation time constants generated by heat in the single firing neuron model produces action potential failures in response to light stimulation. We also found changes in the power spectrum density and a reduction in the time required for synchronization in an interneuron network model of gamma oscillations. Our findings indicate that light stimulation with intensities used in optogenetic experiments may affect neuronal function not only by direct excitation of light sensitive ion channels and/or pumps but also by generating heat. This approach serves as a guide to design optogenetic experiments that minimize the role of tissue heating in the experimental outcome.

Fire Affects Asymbiotic Nitrogen Fixation in Southern Amazon Forests

AbstractIn this study, we investigate the biogeochemical consequences of fire in seasonally flooded Amazon forests, where recent declines in forest cover have been linked to increases in fire frequency and severity. Previous studies have hypothesized that a quasi‐permanent state‐shift transition from typical Amazon forests to open savannas can occur when fire results in further depletion of already impoverished soil nutrient pools. Asymbiotic N2 fixation (ANF) is an essential pathway for fire‐affected forests to acquire nitrogen (N) after disturbance, but ANF response to fire has yet to be quantified in Amazonia. Here, we quantify ANF through field sampling and laboratory incubations using 15N‐labeled dinitrogen (15N2) and measurement of 14 biogeochemical parameters in surface (0–10 cm) and subsurface (10–30 cm) soils. Our data represent burned and unburned replicated sampling sites, across five stands, spanning a gradient from infrequent (once in 13 years) to frequent (five times in 13 years) fire occurrences. ANF did not vary with fire frequency but was, on average, 24% lower in burned than in unburned surface soils across all stands. Burned and unburned subsurface soils had similar ANF rates. About 58% of ANF variance was explained by the joint effect of carbon (C):N ratio and available phosphorus (P) in burned and unburned soils. ANF increased linearly with C:N and P availability in unburned soils, but a highly non‐linear relationship was observed in burned soils. Our findings show that fire alters soil C‐to‐nutrient stoichiometry, which resulted in lower N inputs via ANF into burned relative to unburned tropical forest soils.

What the Blazes!? A People's History of Fire in Labrador

Contemporary fire literature describes past and present fires in Labrador forests as part of a natural and recurrent disturbance regime, with lightning the primary ignition source in an uninhabited wilderness. However, earlier European observers attributed a much larger role to humans in the fire history of a peopled region. According to their historical written accounts, Indigenous peoples and visitors deliberately used fire to manage plant and animal communities, improve soil fertility, and for signalling. These accounts also frequently mention extensive wildfires accidentally set by the observers themselves. Today, Labrador's peoples continue to work with fire in land management, food preservation, and cultural activities. This review considers how relationships with fire in Labrador, both historical and contemporary, interact with lighting-ignited fires to shape ecological patterns in boreal biota; and posits that understanding cultural contributions to fire histories is critical not only in revising unhelpful narratives about an unpeopled Labrador wilderness, but in navigating the future coexistence of fire and people in a boreal zone that is experiencing climate-driven increases in fire frequency and severity.

Ecm29-mediated proteasomal distribution modulates excitatory GABA responses in the developing brain.

Neuronal GABAergic responses switch from excitatory to inhibitory at an early postnatal period in rodents. The timing of this switch is controlled by intracellular Cl- concentrations, but factors determining local levels of cation-chloride cotransporters remain elusive. Here, we report that local abundance of the chloride importer NKCC1 and timely emergence of GABAergic inhibition are modulated by proteasome distribution, which is mediated through interactions of proteasomes with the adaptor Ecm29 and the axon initial segment (AIS) scaffold protein ankyrin G. Mechanistically, both the Ecm29 N-terminal domain and an intact AIS structure are required for transport and tethering of proteasomes in the AIS region. In mice, Ecm29 knockout (KO) in neurons increases the density of NKCC1 protein in the AIS region, a change that positively correlates with a delay in the GABAergic response switch. Phenotypically, Ecm29 KO mice showed increased firing frequency of action potentials at early postnatal ages and were hypersusceptible to chemically induced convulsive seizures. Finally, Ecm29 KO neurons exhibited accelerated AIS developmental positioning, reflecting a perturbed AIS morphological plastic response to hyperexcitability arising from proteasome inhibition, a phenotype rescued by ectopic Ecm29 expression or NKCC1 inhibition. Together, our findings support the idea that neuronal maturation requires regulation of proteasomal distribution controlled by Ecm29.

Erosion analysis of machine gun barrel and lifespan prediction under typical shooting conditions

The operational lifespan of a conventional weapon, such as artillery or machine gun, highly depends on the performance of its barrel. The bore of a machine gun is exposed to erosion as the number of rounds fired increases, which results in continuous increases in barrel diameter and thus an undesired degradation in ballistic performance. In this study, a critical isothermal erosion model for a machine gun barrel is established, and a numerical simulation method is used to study the bore erosion under typical shooting conditions. The current study confirms the presence of thermal-chemical erosion as a predominant failure mechanism at the starting point of the barrel rifling. It is also noted that this thermal-chemical erosion zone expands with the increase in the number of shots fired. Increases in firing frequency, and ambient temperature, and a decrease in the interval between cartridges are found to aggravate the erosion of the barrel bore. By fitting the calculated results, a formula for predicting the maximum erosion at the starting point of the barrel rifling is constructed. The predicted results demonstrate acceptable deviations from the experimental ones, which verify the accuracy and feasibility of the newly developed method in predicting machine gun barrel lifespan.

The small fiber neuropathy NaV1.7 I228M mutation: impaired neurite integrity via bioenergetic and mitotoxic mechanisms, and protection by dexpramipexole.

Gain-of-function variants in voltage-gated sodium channel NaV1.7 that increase firing frequency and spontaneous firing of dorsal root ganglion (DRG) neurons have recently been identified in 5-10% of patients with idiopathic small fiber neuropathy (I-SFN). Our previous in vitro observations suggest that enhanced sodium channel activity can contribute to a decrease in length of peripheral sensory axons. We have hypothesized that sustained sodium influx due to the expression of SFN-associated sodium channel variants may trigger an energetic deficit in neurons that contributes to degeneration and loss of nerve fibers in SFN. Using an ATP FRET biosensor, we now demonstrate reduced steady-state levels of ATP and markedly faster ATP decay in response to membrane depolarization in cultured DRG neurons expressing an SFN-associated variant NaV1.7, I228M, compared with wild-type neurons. We also observed that I228M neurons show a significant reduction in mitochondrial density and size, indicating dysfunctional mitochondria and a reduced bioenergetic capacity. Finally, we report that exposure to dexpramipexole, a drug that improves mitochondrial energy metabolism, increases the neurite length of I228M-expressing neurons. Our data suggest that expression of gain-of-function variants of NaV1.7 can damage mitochondria and compromise cellular capacity for ATP production. The resulting bioenergetic crisis can consequently contribute to loss of axons in SFN. We suggest that, in addition to interventions that reduce ionic disturbance caused by mutant NaV1.7 channels, an alternative therapeutic strategy might target the bioenergetic burden and mitochondrial damage that occur in SFN associated with NaV1.7 gain-of-function mutations.NEW & NOTEWORTHY Sodium channel NaV1.7 mutations that increase dorsal root ganglion (DRG) neuron excitability have been identified in small fiber neuropathy (SFN). We demonstrate reduced steady-state ATP levels, faster depolarization-evoked ATP decay, and reduced mitochondrial density and size in cultured DRG neurons expressing SFN-associated variant NaV1.7 I228M. Dexpramipexole, which improves mitochondrial energy metabolism, has a protective effect. Because gain-of-function NaV1.7 variants can compromise bioenergetics, therapeutic strategies that target bioenergetic burden and mitochondrial damage merit study in SFN.

Multi-scale habitat selection by Northern Goshawks (Accipiter gentilis) in a fire-prone forest

Increasing frequency and severity of wildfire may jeopardize persistence of large tracts of late seral forest, raising concerns over population viability of forest-dependent species like the Northern Goshawk (Accipiter gentilis). We tracked 20 adult Northern Goshawks with GPS loggers over 4 years to investigate roosting (nocturnal) and foraging (diurnal) habitat selection in a heterogeneously burned forest landscape of the Sierra Nevada mountains of California, United States. Goshawks selected late seral forest attributes for both roosting and foraging at multiple spatio-temporal scales, although at the finest (daily) scale, goshawks selected more diverse forest structure that included small trees and medium canopy cover. Less than 6% of roosts were in areas burned in the last 50 years and goshawks avoided areas burned at high severity when roosting and when foraging across spatial scales. Four goshawks (3 males, 1 female) undertook forays >5 km from their nest location, two of which forayed into burned areas during at least one season. High severity fire is likely to make forests unsuitable foraging or roosting habitat for Northern Goshawks, although lower severity fire may provide foraging opportunities for this generalist predator. Eighty percent of foraging space use and 87% of roost locations were considered high fire hazard potential, suggesting that goshawk habitat in western North America is likely to be reduced by predicted increases in fire frequency and severity in the region.

Long-term effects of forest fires on soil greenhouse gas emissions and extracellular enzyme activities in a hemiboreal forest

Fire is the most important natural disturbance in boreal forests, and it has a major role regulating the carbon (C) budget of these systems. With the expected increase in fire frequency, the greenhouse gas (GHG) budget of boreal forest soils may change. In order to understand the long-term nature of the soil–atmosphere GHG exchange after fire, we established a fire chronosequence representing successional stages at 8, 19, 34, 65, 76 and 179 years following stand-replacing fires in hemiboreal Scots pine forests in Estonia. Changes in extracellular activity, litter decomposition, vegetation biomass, and soil physicochemical properties were assessed in relation to carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) emissions. Soil temperature was highest 8 years after fire, whereas soil moisture varied through the fire chronosequences without a consistent pattern. Litter decomposition and CO2 efflux were still lower 8 years after fire compared with pre-fire levels (179 years after fire). Both returned to pre-fire levels before vegetation re-established, and CO2 efflux was only strongly responsive to temperature from 19 years after fire onward. Recovery of CO2 efflux in the long term was associated with a moderate effect of fire on enzyme activity, the input of above- and below-ground litter carbon, and the re-establishment of vegetation. Soil acted as a CH4 sink and N2O source similarly in all successional stages. Compared with soil moisture and time after fire, soil temperature was the most important predictor for both GHGs. The re-establishment of overstorey and vegetation cover (mosses and lichens) might have caused an increase in CH4 and N2O effluxes in the studied areas, respectively.