The parameters of the stochastic leaky integrate-and-fire neuronal model

Five parameters of one of the most common neuronal models, the diffusion leaky integrate-and-fire model, also known as the Ornstein-Uhlenbeck neuronal model, were estimated on the basis of intracellular recording. These parameters can be classified into two categories. Three of them (the membrane time constant, the resting potential and the firing threshold) characterize the neuron itself. The remaining two characterize the neuronal input. The intracellular data were collected during spontaneous firing, which in this case is characterized by a Poisson process of interspike intervals. Two methods for the estimation were applied, the regression method and the maximum-likelihood method. Both methods permit to estimate the input parameters and the membrane time constant in a short time window (a single interspike interval). We found that, at least in our example, the regression method gave more consistent results than the maximum-likelihood method. The estimates of the input parameters show the asymptotical normality, which can be further used for statistical testing, under the condition that the data are collected in different experimental situations. The model neuron, as deduced from the determined parameters, works in a subthreshold regimen. This result was confirmed by both applied methods. The subthreshold regimen for this model is characterized by the Poissonian firing. This is in a complete agreement with the observed interspike interval data. Action Editor: Nicolas Brunel     

Analysis of a stochastic neuronal model with excitatory inputs and state-dependent effects

We propose a stochastic model for the firing activity of a neuronal unit. It includes the decay effect of the membrane potential in absence of stimuli, and the occurrence of time-varying excitatory inputs governed by a Poisson process. The sample-paths of the membrane potential are piecewise exponentially decaying curves with jumps of random amplitudes occurring at the input times. An analysis of the probability distributions of the membrane potential and of the firing time is performed. In the special case of time-homogeneous stimuli the firing density is obtained in closed form, together with its mean and variance.     

Attentional modulation of firing rate and synchrony in a model cortical network

The response of a neuron in the visual cortex to stimuli of different contrast placed in its receptive field is commonly characterized using the contrast response curve. When attention is directed into the receptive field of a V4 neuron, its contrast response curve is shifted to lower contrast values (Reynolds et al., 2000). The neuron will thus be able to respond to weaker stimuli than it responded to without attention. Attention also increases the coherence between neurons responding to the same stimulus (Fries et al., 2001). We studied how the firing rate and synchrony of a densely interconnected cortical network varied with contrast and how they were modulated by attention. The changes in contrast and attention were modeled as changes in driving current to the network neurons. We found that an increased driving current to the excitatory neurons increased the overall firing rate of the network, whereas variation of the driving current to inhibitory neurons modulated the synchrony of the network. We explain the synchrony modulation in terms of a locking phenomenon during which the ratio of excitatory to inhibitory firing rates is approximately constant for a range of driving current values. We explored the hypothesis that contrast is represented primarily as a drive to the excitatory neurons, whereas attention corresponds to a reduction in driving current to the inhibitory neurons. Using this hypothesis, the model reproduces the following experimental observations: (1) the firing rate of the excitatory neurons increases with contrast; (2) for high contrast stimuli, the firing rate saturates and the network synchronizes; (3) attention shifts the contrast response curve to lower contrast values; (4) attention leads to stronger synchronization that starts at a lower value of the contrast compared with the attend-away condition. In addition, it predicts that attention increases the delay between the inhibitory and excitatory synchronous volleys produced by the network, allowing the stimulus to recruit more downstream neurons. Action Editor: David Golomb     

Effects of two estradiol esters (benzoate and cypionate) on the induction of synchronized ovulations in Bos indicus cows submitted to a timed artificial insemination protocol

The effects of estradiol benzoate (EB) and estradiol cypionate (EC) on induction of ovulation after a synchronized LH surge and on fertility of Bos indicus females submitted to timed AI (TAI) were evaluated. In Experiment 1, ovariectomized Nelore heifers were used to evaluate the effect of EB (n = 5) and EC (n = 5) on the circulating LH profile. The LH surge timing (19.6 and 50.5 h; P = 0.001), magnitude (20.5 and 9.4 ng/mL; P = 0.005), duration (8.6 and 16.5 h; P = 0.001), and area under the LH curve (158.6 and 339.4 ng/mL; P = 0.01) differed between the EB and EC treatments, respectively. In Experiment 2 (follicular responses; n = 60) and 3 (pregnancy per AI; P/AI; n = 953) suckled Bos indicus beef cows submitted to an estradiol/progesterone-based synchronization protocol were assigned to receive one of two treatments to induce synchronized ovulation: 1 mg of EB im 24 h after progesterone (P4) device removal or 1 mg of EC im at P4 device removal. There was no difference (P > 0.05) between EB and EC treatments on follicular responses (maximum diameter of the ovulatory follicle, 13.1 vs. 13.9 mm; interval from progesterone device removal to ovulation, 70.2 vs. 68.5 h; and ovulation rate, 77.8 vs. 82.8%, respectively). In addition, P/AI was similar (P < 0.22) between the cows treated with EB (57.5%; 277/482) and EC (61.8%; 291/471). In conclusion, despite pharmacologic differences, both esters of estradiol administered either at P4 device removal (EC) or 24 h later (EB) were effective in inducing an LH surge which resulted in synchronized ovulations and similar P/AI in suckled Bos indicus beef cows submitted to TAI.     

Episodic stemflow inputs of magnesium and potassium to a tropical forest floor during heavy rainfall events

Summary Stemflow inputs of magnesium and potassium were measured from 57 canopy trees representing eight species under heavy rainfall conditions in two tropical forest sites in northeast Queensland, Australia. In the premontane tropical moist forest site on the Atherton Tableland, the stemflow input per unit trunk basal area of 51 canopy trees was found to be 0.46 g m^-2 of Mg²⁺ and 4.22 g m^-2 of K⁺ for an average wet season rainday of 99 mm. In the wetter montane tropical rainforest site on Mount Bellenden Ker, the stemflow input per unit trunk basal area of six canopy trees was 5.55 g m^-2 of Mg²⁺ and 9.12 g m^-2 of K⁺ for a wet season rainday of 38 mm. These stemflow inputs from single raindays are greater than the mean annual rainfall input and are almost of the same order of magnitude as the mean annual throughfall input of these cations to areas equal to the trunk basal area from which the stemflow was collected. Stemflow cation fluxes of this magnitude are mainly attributable to the funnelling of large quantities of rainwater down the trunks of these canopy trees by their thoroughly wetted, upwardly inclined branches.     

亚热带米槠天然林凋落物和根系输入变化对土壤磷组分的影响

植物残体添加和去除试验(The Detritus Input and Removal Treatments, DIRT)是研究地上凋落物以及植物根系对土壤营养物质循环过程及机制探究的一种试验设计。于2012年6月选择福建省三明森林生态系统与全球变化研究站的米槠常绿阔叶天然林,设置5种处理:对照(CT)、去除凋落物(NL)、去除根系(NR)、去除凋落物与根系(NI)、添加双倍凋落物(DL),在2018年12月对各处理不同土层(0—10cm、10—20cm)土壤磷组分及其影响因子进行研究,结果表明:(1)在0—10cm土层中DL处理总磷含量显著大于NL处理,NI处理无机磷含量最低,在10—20cm中DL处理有机磷含量显著大于其他处理;(2)DL处理活性磷(Resin-P、NaHCO₃-Pi、NaHCO₃-Po)含量在0—10cm土层中显著大于其他处理。在10—20cm土层中NR处理活性磷以及中等活性磷显著大于NL处理。残留态磷(Residual-P)含量最高,但在各处理与土层之间并没有明显差异;(3)酸性磷酸酶在0—10 cm土层不同处理间的变化...     

Generalized estimating equations: A pragmatic and flexible approach to the marginal GLM modelling of correlated data in the behavioural sciences

Within behavioural research, non‐normally distributed data with a complicated structure are common. For instance, data can represent repeated observations of quantities on the same individual. The regression analysis of such data is complicated both by the interdependency of the observations (response variables) and by their non‐normal distribution. Over the last decade, such data have been more and more frequently analysed using generalized mixed‐effect models. Some researchers invoke the heavy machinery of mixed‐effect modelling to obtain the desired population‐level (marginal) inference, which can be achieved by using simpler tools—namely by marginal models. This paper highlights marginal modelling (using generalized estimating equations [GEE]) as an alternative method. In various situations, GEE can be based on fewer assumptions and directly generate estimates (population‐level parameters) which are of immediate interest to the behavioural researcher (such as population means). Using four examples from behavioural research, we demonstrate the use, advantages, and limits of the GEE approach as implemented within the functions of the ‘geepack’ package in R.     

Sources,fates, and impacts of nitrogen inputs to terrestrial ecosystems: review and synthesis

The relative importance of nitrogen inputs from atmospheric deposition and biological fixation is reviewed in a number of diverse, non-agricultural terrestrial ecosystems. Bulk precipitation inputs of N (l–l2 kg N ha^–1 yr^–1) are the same order of magnitude as, or frequently larger than, the usual range of inputs from nonsymbiotic fixation (< 1=" –=" 5=" kg=" n=">^–1 yr^–1), especially in areas influenced by industrial activity. Bulk precipitation measurements may underestimate total atmospheric deposition by 30–40% because they generally do not include all forms of wet and dry deposition. Symbiotic fixation generally ranges from 10–160 kg N ha^–1 yr^–1) in ecosystems where N-fixing species are present during early successional stages, and may exceed the range under unusual conditions.Rates of both symbiotic and nonsymbiotic fixation appear to be greater during early successional stages of forest development, where they have major impacts on nitrogen dynamics and ecosystem productivity. Fates and impacts of these nitrogen inputs are important considerations that are inadequately understood. These input processes are highly variable in space and time, and few sites have adequate comparative information on both nitrogen deposition and fixation.

Food availability and parasite infection influence the correlated responses of life history traits to selection for age at pupation in the mosquito Aedes aegypti

We selected six lines of mosquito Aedes aegypti for earlier or later pupation and measured the correlated responses of several life history traits: adult size, two fecundity measures and pre-adult survival. We further examined the influence of two environmental parameters – larval food availability and infection by the microsporidian parasite Edhazardia aedis– on the correlated responses. Pre-adult survival did not respond to selection for age at pupation in any environment. For all of the other traits, the environment influenced the correlated response, though the contribution of the different environmental aspects differed among traits. While the correlated response of adult size was influenced only by larval food availability, the likelihood that a female laid eggs was influenced by parasite infection, and the correlated response of the number of eggs was influenced by the interaction of the two environmental parameters. Generally, a deteriorating environment moved the correlated response from one favouring later pupation to one favouring earlier pupation. Larval food availability and parasite infection also influenced the association between the mean wing length and fecundity of the selected lines. At high food availability, there was a positive relationship between adult size and fecundity, while infected mosquitoes reared at low food availability showed the opposite trend. We discuss these results in light of the coevolutionary potential of the host–parasite interaction.     

亚热带典型森林地上和地下凋落物输入对土壤新老有机碳动态平衡的影响

凋落物是森林土壤有机碳(SOC)形成、稳定和周转的重要影响因子。目前针对亚热带不同类型森林地上和地下凋落物对新SOC累积和老SOC输出动态平衡的影响仍不清楚。本研究以中亚热带常绿阔叶天然林、马尾松人工林和杉木人工林为对象,基于C3/C4植物-土壤置换试验,利用稳定同位素¹³C示踪方法开展3年野外定位试验,分析了森林地上、地下凋落物输入对SOC周转的影响。结果表明: 森林类型、凋落物处理和时间均能显著影响SOC含量、土壤δ¹³C值、新SOC和老SOC含量,且存在显著的森林类型×凋落物处理交互效应。地上和地下凋落物输入均能显著提高SOC含量和净增量,与杉木人工林相比,天然林SOC对凋落物输入的响应更敏感。凋落物输入显著降低了土壤δ¹³C值,且天然林、马尾松人工林土壤δ¹³C显著低于杉木人工林。在马尾松人工林,地下凋落物处理的新SOC含量显著高于地上凋落物;在天然林和马尾松人工林,地下凋落物输入处理的老SOC含量显著低于地上凋落物处理。此外,地上凋落物归还量和地下根生物量与SOC含量和净增量呈显著正相关,而地下根凋落物量和C/N与新SOC含量呈显著正相关。森林地下凋落物比地上凋落物输入对SOC周转的影响更重要,且不同森林凋落物输入对SOC的影响存在差异性。本研究可为揭示亚热带典型森林土壤有机碳库的形成和可持续管理提供依据。     

Effective epitope identification employing phylogenetic,mutational variability,sequence entropy,and correlated mutation analysis targeting NS5B protein of hepatitis C virus: from bioinformatics to therapeutics

Hepatitis C virus (HCV) is considered as a foremost cause affecting numerous human liver‐related disorders. An effective immuno‐prophylactic measure (like stable vaccine) is still unavailable for HCV. We perform an in silico analysis of nonstructural protein 5B (NS5B) based CD4 and CD8 epitopes that might be implicated in improvement of treatment strategies for efficient vaccine development programs against HCV. Here, we report on effective utilization of knowledge obtained from multiple sequence alignment and phylogenetic analysis for investigation and evaluation of candidate epitopes that have enormous potential to be used in formulating proficient vaccine, embracing multiple strains prevalent among major geographical locations. Mutational variability data discussed herein focus on discriminating the region under active evolutionary pressure from those having lower mutational potential in existing experimentally verified epitopes, thus, providing a concrete framework for designing an effective peptide‐based vaccine against HCV. Additionally, we measured entropy distribution in NS5B residues and pinpoint the positions in epitopes that are more susceptible to mutations and, thus, account for virus strategy to evade the host immune system. Findings from this study are expected to add more details on the sequence and structural aspects of NS5B protein, ultimately facilitating our understanding about the pathophysiology of HCV and assisting advance studies on the function of NS5B antigen on the epitope level. We also report on the mutational crosstalk between functionally important coevolving residues, using correlated mutation analysis, and identify networks of coupled mutations that represent pathways of allosteric communication inside and among NS5B thumb, finger, and palm domains. Copyright © 2015 John Wiley & Sons, Ltd.     

Knockdown resistance to dichlorodiphenyl-trichloroethane and pyrethroid insecticides in the napts mutant of Drosophila melanogaster is correlated with reduced neuronal sensitivity

Resistance to pyrethroid insecticides and dichlorodiphenyltrichloroethane (DDT) was investigated in the nap^ts (no action potential, temperature sensitive) mutant of Drosophila melanogaster. In surface contact bioassays, the nap^ts strain showed threefold resistance to deltamethrin at the LC₅₀ level when compared to susceptible Canton-S flies. Cross-resistance was also observed to DDT and the pyrethroids NRDC 157 [3-phenoxybenzyl [1R,cis]-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate], fenfluthrin, and MTI-800 [1-(3-phenoxy-4-fluorophenyl)-4-(4-ethoxyphenyl)-4-methylpentane]. The onset of intoxication by pyrethroids in nap^ts flies was markedly delayed, a finding that is consistent with the existence of a resistance mechanism involving reduced neuronal sensitivity. Resistance at the level of the nerve was confirmed by electrophysiological recordings of spontaneous and evoked activity in the dorsolongitudinal flight muscles of poisoned flies. Preparations from nap^ts insects treated with fenfluthrin displayed longer latencies to the appearance of spontaneous activity and also an absence or reduction in burst discharges compared to equivalent preparations from susceptible individuals. These results are discussed in light of competing hypotheses concerning the mechanism underlying knockdown resistance and reduced nerve sensitivity in insects.     

A stochastic model of tree architecture and biomass partitioning: application to Mongolian Scots pines

Background and Aims

Mongolian Scots pine (Pinus sylvestris var. mongolica) is one of the principal species used for windbreak and sand stabilization in arid and semi-arid areas in northern China. A model-assisted analysis of its canopy architectural development and functions is valuable for better understanding its behaviour and roles in fragile ecosystems. However, due to the intrinsic complexity and variability of trees, the parametric identification of such models is currently a major obstacle to their evaluation and their validation with respect to real data. The aim of this paper was to present the mathematical framework of a stochastic functional–structural model (GL2) and its parameterization for Mongolian Scots pines, taking into account inter-plant variability in terms of topological development and biomass partitioning.

Methods

In GL2, plant organogenesis is determined by the realization of random variables representing the behaviour of axillary or apical buds. The associated probabilities are calibrated for Mongolian Scots pines using experimental data including means and variances of the numbers of organs per plant in each order-based class. The functional part of the model relies on the principles of source–sink regulation and is parameterized by direct observations of living trees and the inversion method using measured data for organ mass and dimensions.

Key Results

The final calibration accuracy satisfies both organogenetic and morphogenetic processes. Our hypothesis for the number of organs following a binomial distribution is found to be consistent with the real data. Based on the calibrated parameters, stochastic simulations of the growth of Mongolian Scots pines in plantations are generated by the Monte Carlo method, allowing analysis of the inter-individual variability of the number of organs and biomass partitioning. Three-dimensional (3D) architectures of young Mongolian Scots pines were simulated for 4-, 6- and 8-year-old trees.

Conclusions

This work provides a new method for characterizing tree structures and biomass allocation that can be used to build a 3D virtual Mongolian Scots pine forest. The work paves the way for bridging the gap between a single-plant model and a stand model.     

A stochastic model of tumor response to fractionated radiation: limit theorems and rate of convergence

The iterated birth and death Markov process is defined as an n-fold iteration of a birth and death Markov process describing kinetics of certain population combined with random killing of individuals in the population at moments tau 1,...,tau n with given survival probabilities s1,...,sn. A long-standing problem of computing the distribution of the number of clonogenic tumor cells surviving an arbitrary fractionated radiation schedule is solved within the framework of iterated birth and death Markov process. It is shown that, for any initial population size iota, the distribution of the size N of the population at moment t > or = tau n is generalized negative binomial, and an explicit computationally feasible formula for the latter is found. It is shown that if i --> infinity and sn --> 0 so that the product iota s1...sn tends to a finite positive limit, the distribution of random variable N converges to a probability distribution, which for t = tau n turns out to be Poisson. In the latter case, an estimate of the rate of convergence in the total variation metric similar to the classical Law of Rare Events is obtained.     

Effects of warmer world scenarios on hydrologic inputs to Lake Mälaren,Sweden and implications for nutrient loads

A simple, rapid, and flexible modelling approach was applied to explore the impacts of climate change on hydrologic inputs and consequent implications for nutrient loading to Lake Mälaren, Sweden using a loading function model (GWLF). The first step in the process was to adapt the model for use in a large and complex Swedish catchment. We focused on the Galten basin with four rivers draining into the western region of Mälaren. The catchment model was calibrated and tested using long-term historical data for river discharge and dissolved nutrients (N, P). Then multiple regional climate model simulation results were downscaled to the local catchment level, and used to simulate possible hydrological and nutrient loading responses to warmer world scenarios. Climate change projections for the rivers of Galten basin show profound changes in the timing of discharge and nutrient delivery due to increased winter precipitation and earlier snow melt. Impacts on total annual discharge and load are minimal, but the alteration in river flow regime and the timing of nutrient delivery for future climate scenarios is strikingly different from historical conditions.     

Effects of ischemic post‐conditioning on neuronal VEGF regulation and microglial polarization in a rat model of focal cerebral ischemia

Ischemic postconditioning is increasingly being investigated as a therapeutic approach for cerebral ischemia. However, the majority of studies are focused on the acute protection of neurons per se . Whether and how postconditioning affects multiple cells in the recovering neurovascular unit remains to be fully elucidated. Here, we asked whether postconditioning may modulate help‐me signaling between injured neurons and reactive microglia. Rats were subjected to 100 min of focal cerebral ischemia, then randomized into a control versus postconditioning group. After 3 days of reperfusion, infarct volumes were significantly reduced in animals treated with postconditioning, along with better neurologic outcomes. Immunostaining revealed that ischemic postconditioning increased expression of vascular endothelial growth factor (VEGF ) in neurons within peri‐infarct regions. Correspondingly, we confirmed that VEGFR 2 was expressed on Iba1‐positive microglia/macrophages, and confocal microscopy showed that in postconditioned rats, these cells were polarized to a ramified morphology with higher expression of M2‐like markers. Treating rats with a VEGF receptor 2 kinase inhibitor negated these effects of postconditioning on microglia/macrophage polarization. In vitro , postconditoning after oxygen‐glucose deprivation up‐regulated VEGF release in primary neuron cultures, and adding VEGF to microglial cultures partly shifted their M2‐like markers. Altogether, our findings support the idea that after postconditioning, injured neurons may release VEGF as a ‘help‐me’ signal that promotes microglia/macrophage polarization into potentially beneficial phenotypes.

     

A discrete,stochastic model of colonial phytoplankton population size structure: Development and application to in situ imaging-in-flow cytometer observations of Dinobryon

The scientific community lacks models for the dynamic changes in population size structure that occur in colonial phytoplankton. This is surprising, as size is a key trait affecting many aspects of phytoplankton ecology, and colonial forms are very common. We aim to fill this gap with a new discrete, stochastic model of dynamic changes in phytoplankton colonies' population size structure. We use the colonial phytoplankton Dinobryon as a proof-of-concept organism. The model includes four stochastic functions—division, stomatocyst production, colony breakage, and colony loss—to determine Dinobryon population size structure and populations counts. Although the functions presented here are tailored to Dinobryon, the model is readily adaptable to represent other colonial taxa. We demonstrate how fitting our model to in situ observations of colony population size structure can provide a powerful approach to explore colony size dynamics. Here, we have (1) collected high-frequency in situ observations of Dinobryon in Lac (Lake) Montjoie (Quebec, Canada) in 2013 with a moored Imaging FlowCytobot (IFCB) and (2) fit the model to those observations with a genetic algorithm solver that extracts parameter estimates for each of the four stochastic functions. As an example of the power of this model-data integration, we also highlight ecological insights into Dinobryon colony size and stomatocyst production. The Dinobryon population was enriched in larger, flagellate-rich colonies near bloom initiation and shifted to smaller and emptier colonies toward bloom decline.     

Amphibian larvae and zinc sulphate: a suitable model to study the role of brain-derived neurotrophic factor (BDNF) in the neuronal turnover of the olfactory epithelium

The vertebrate olfactory system has fascinated neurobiologists over the last six decades because of its ability to replace its neurons and synaptic connections continuously throughout adult life, under both physiological and pathological conditions. Among the factors that are proposed to be involved in this regenerative potential, brain-derived neurotrophic factor (BDNF) is a candidate for having an important role in the neuronal turnover in the olfactory epithelium (OE) because of its well-documented neurogenic and trophic effects throughout the nervous system. The aim of the present study was to generate a suitable model to study the participation of BDNF in the recovery of the OE after injury in vivo. We developed an experimental design in which the OE of Rhinella arenarum tadpoles could be easily and selectively damaged by immersing the animals in ZnSO₄ solutions of various concentrations for differing time periods. Image analysis of histological sections showed that different combinations of each of these conditions produced statistically different degrees of injury to the olfactory tissue. We also observed that the morphology of the OE was restored within a few days of recovery after ZnSO₄ treatment. Immunohistochemical analysis of BDNF was performed with an antiserum whose specificity was confirmed by Western blotting, and which showed drastic changes in the abundance and distribution pattern of this neurotrophin in the damaged olfactory system. Our results thus suggest that BDNF is involved in the regeneration of the OE of amphibian larvae, and that our approach is suitable for further investigations of this topic. This work was supported by grants from CONICET (PIP 5842), Universidad de Buenos Aires (UBACYT X131) and ANPCYT (PICT 32219).