Symmetric bursting behaviors in the generalized FitzHugh–Nagumo model

In the current paper, we have investigated the generalized FitzHugh–Nagumo model. We have shown that symmetric bursting behaviors of different types could be observed in this model with an appropriate recovery term. A modified version of this system is used to construct bursting activities. Furthermore, we have shown some numerical examples of delayed Hopf bifurcation and canard phenomenon in the symmetric bursting of super-Hopf/homoclinic type near its super-Hopf and homoclinic bifurcations, respectively.     

Rotating wave solutions of the FitzHugh–Nagumo equations

This paper will treat the bifurcation and numerical simulation of rotating wave (RW) solutions of the FitzHugh-Nagumo (FHN) equations. These equations are often used as a simple mathematical model of excitable media. The dependence of the solutions on a uniformly applied current, and also on the diffusion coefficients or domain size will be studied. Ranges of applied current and/or diffusion coefficients in which RW solutions are observed will be described using bifurcation theory and continuation methods. The bifurcation of time-periodic solutions of these FHN equations without diffusion is described first. Similar methods are then used to find RW solutions on a circular ring and numerical simulations are described. These results are then extended to investigate RW solutions on annular rings of finite cross-section. Scaling arguments are used to show how the existence of solutions depends on either the diffusion coefficient or on the size of the region.     

Reconstructing parameters of the FitzHugh–Nagumo system from boundary potential measurements

We consider distributed parameter identification problems for the FitzHugh–Nagumo model of electrocardiology. The model describes the evolution of electrical potentials in heart tissues. The mathematical problem is to reconstruct physical parameters of the system through partial knowledge of its solutions on the boundary of the domain. We present a parallel algorithm of Newton–Krylov type that combines Newton’s method for numerical optimization with Krylov subspace solvers for the resulting Karush–Kuhn–Tucker system. We show by numerical simulations that parameter reconstruction can be performed from measurements taken on the boundary of the domain only. We discuss the effects of various model parameters on the quality of reconstructions. Action Editor: David Terman     

Weak phylogenetic signal for specialisation in antagonistic liana–tree networks

Background: Antagonistic interactions, such as parasitism and herbivory, are generally specialised and have a strong phylogenetic signal for specialisation. As lianas and trees interact antagonistically, we expect to find phylogenetic signal for specialisation.

Aims: We aimed to answer the following questions: (1) Is the liana–tree network specialised? (2) Is the specialisation of liana–tree network related to the abundance of both the life forms? (3) Is liana and tree specialisation related to species phylogeny? (4) Do phylogenetically related liana species occupy phylogenetically related tree species, and vice versa?

Methods: For three areas in southern Brazil, we calculated the specialisation value of each liana and tree species (d') and of the entire network (H₂′). Binomial regression and null models were used to test the role of abundance on d' and H₂′, respectively. We searched for the presence of phylogenetic signal with phylogenetic independent contrasts for d'. We also compared the similarity of species sets and their interaction with phylogenetic distance between them using Mantel test.

Results: All three networks had significant values of H₂′, but the values of d' did not have significant phylogenetic signals. Closely related lianas did not share similar host-tree assemblages and vice versa. Rare species were more specialised than abundant species, and abundance did not influence H₂′.

Conclusions: Our study indicates that the significant H₂′ may be due to co-evolution in some lineages of lianas and trees. Nevertheless, the abundance of species may also play an important role in species interaction, mainly rare species.     

Stochastic resonance and signal detection in an energy detector – implications for biological receptor systems

Stochastic resonance is demonstrated in a simple energy detector model, as a non-monotonic relationship between signal-to-noise ratio and detection of a sinusoid signal in bandpass-limited Gaussian noise. The behaviour of the model detecting signals of various intensities and signal-to-noise ratios was investigated. Significant improvement in detection was obtained by adding noise for mean signal intensities below the detection criterion of the detector. The range of usable noise levels, however, may be too small to be biologically meaningful. It is demonstrated that improving detection in the analysed model by adding noise to an otherwise undetectable signal is only at best as efficient as what can be obtained by adjusting the criterion to the signal-to-noise ratio. Improving detection by means of stochastic resonance is thus a sub-optimal strategy. It is speculated whether a demonstration of stochastic resonance in a biological system indicates any adaptive significance. More than anything, it indicates the presence of a mismatch between receptor sensitivity and the signal-to-noise ratio of the experiment, not the cause of this mismatch. Received: 22 December 1999 / Accepted in revised form: 14 April 2000     

Ultrasound detection in fish--a parallel to the sonar-mediated detection of bats by ultrasound-sensitive insects?

Most bats use ultrasonic sonar signals, or cries, to locate prey. Many of their insect prey species have evolved an ability to hear and respond to these signals, and studies clearly demonstrate the survival value associated with this ability. Like bats, toothed whales locate prey by emitting ultrasonic sonar signals, or clicks. As a parallel to the insect prey of bats, it would seem obvious to assume that some fish species likewise are capable of sensing the ultrasonic clicks of their odontocete predators. As judged from classical fish audiometry literature, this seems not to be the case, however, and although in recent years some fishes have been proven responsive to ultrasound, examination of ecological and acoustic differences reveals that conclusions on ultrasound-mediated insect escape behavior are not immediately applicable to fish. This has the consequence that future experiments on fish ultrasound detection should not be looking for observations directly parallel to those observed in the bat-insect interactions.     

Citrinin detection by intensified fluorescence signal of a FRET-based immunosensor using magnetic/silica core–shell

The specific immune-reaction between the anti-citrinin antibody immobilized on the surface of magnetic/silica core–shell (MSCS) and the citrinin–Rho123–BSA conjugate brings the Rho123 fluorophore as an acceptor and the QDs as a donor in close spatial proximity and causes FRET for occurring upon photo-excitation of the QDs. The novelties of this study include: (1) immobilization of the MSCS; (2) large amount of the immobilized QDs, and (3) immobilization of a large amount of Rho123 on the BSA macromolecule. Cd/Te QDs were synthesized by the simultaneous reduction of cadmium chloride and tellurium in the presence of sodium borohydride. Magnetic nanoparticles were synthesized using FeSO₄ and FeCl₃. The prepared magnetic nanoparticles shelled by silica using tetraethoxysilane in the presence of ammonia. Transmission electron microscopy (TEM) analysis was used for investigating shape and monodispersity of the nanoparticles. EDC/NHS was used as a cross linking agent for immobilization of the QDs, conjugation of citrinin to amino groups of BSA, labeling of BSA with Rho123 and also for immobilization of the amino-functionalized MSCS on the immobilized QDs. Immobilization of the anti-citrinin antibody on the surface of the amino-functionalized MSCS was performed by Schiff-base mechanism. By using these three effective strategies, sensitivity of the designed nanobiosensor was incredibly enhanced as a very low limit of detection (up to 0.1 pM). The feasibility of this technique was tested by the detection of citrinin in the spiked human serum. Results showed that there was a linear correlation between the decreased fluorescence intensity of the Rho123 and increased fluorescence intensity of the QDs with increasing concentration of citrinin in the spiked samples in the range of 1–6 pM. According to obtained results, we conclude that this highly sensitive detection scheme is a easy, quick and impressive method that can be used in optical-based nanosensors.     

Validated method for the determination of hydroquinone in human urine by high-performance liquid chromatography–coulometric-array detection

The paper describes the computer aided method development and validation for the determination of hydroquinone in human urine from a clinical study on renal excretion of hydroquinone metabolites and the release of free hydroquinone in the urinary tract in order to evaluate the proposed urine disinfecting concept. The presented method uses high-performance liquid chromatography on reversed-phase material with a polar endcapping (Aqua-C₁₈, 250×4.6 mm). Selective and sensitive determination (LOQ=12.5 ng on-column) of the target compound was achieved by electrochemical array detection (CoulArray). Gradient and parameter optimization were supported by DryLab software in order to minimize efforts of the expensive and time-consuming method development. Specificity and selectivity were carried out by separation experiments involving the prodrug arbutin and the metabolites hydroquinone, hydroquinone glucuronide, and hydroquinone sulfate, respectively. Hydroquinone glucuronide reference standard was obtained from in vitro glucuronidation in a rat liver microsomes assay. The method was validated according to the criteria for validation of pharmaceutical bioanalytical methods as drafted by the US Department of Health and Human Services, 1998.     

Supersensitive detection of T-2 toxin by the in situ synthesized π-conjugated molecularly imprinted nanopatterns. An in situ investigation by surface plasmon resonance combined with electrochemistry

A π-conjugated molecularly imprinted polymer (MIP) with nanopatterns for T-2 toxin (T-2) was prepared on SPR chip by in situ electropolymerization of 3-aminophenylboronicacid (3-APBA) with T-2. The complete removal of T-2 from polymer was confirmed in situ by SPR and EIS and also ex situ by SEM, EDAX, fluorescence microscopy and Raman spectroscopy. SEM image of T-2 MIP exhibited nanopatterns due to imprinting of T-2. The MIP of T-2 showed a linear response for T-2 from 2.1 fM to 33.6 fM with a detection limit of 0.1 fM (0.05 pg/mL). In this study, thermodynamic parameters such as change in Gibb's free energy (ΔG), change in enthalpy (ΔH) and change in entropy (ΔS) were determined and the values revealed that the interaction between T-2 and T-2 MIP as spontaneous, endothermic and entropy driven one. Moreover, interactions of very high concentration of interferents with T-2 MIP showed very less response due to the presence of nanopatterns of T-2 in the T-2 MIP. Equilibrium constant (12.7 fM) obtained in this study indicates the super binding affinity of T-2 with T-2 MIP. Moreover, the present methodology provides an outline to develop field-detection equipment capable of detecting T-2 toxin at or well below the guideline concentrations recommended by American subcommittee on military field drinking water.     

PPARγ signal transduction pathway in the foam cell formation induced by visfatin

The aim of the present study was to investigate the role of peroxisome proliferator-activated receptor γ (PPARγ) signal transduction pathway in the expression of ATP binding cassette transporter A1 (ABCA1) and acyl-CoA:cholesterol acyltransferase 1 (ACAT1) induced by visfatin and to discuss the mechanism of foam cell formation induced by visfatin. THP-1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate (PMA) for 48 h, and then the macrophages were exposed to visfatin and PPARγ activator rosiglitazone, respectively. The expressions of PPARγ, ABCA1 and ACAT1 mRNA and protein were determined by RT-PCR and Western blot respectively. The contents of total cholesterol (TC) and free cholesterol (FC) were detected by enzyme fluorescence analysis. The content of cholesterol ester (CE) was calculated by the difference between TC and FC. The results showed that visfatin decreased the mRNA and protein expressions of PPARγ and ABCA1, increased the mRNA and protein expressions of ACAT1, and increased the contents of FC and CE in a concentration-dependent manner. These above effects of visfatin were inhibited by rosiglitazone in a concentration-dependent manner. These results suggest that visfatin may down-regulate the ABCA1 expression and up-regulate the ACAT1 expression via PPARγ signal transduction pathway, which decreases the outflow of FC, increases the content of CE, and then induces foam cell formation.     

Weak protein–protein interactions revealed by immiscible filtration assisted by surface tension

Biological mechanisms are often mediated by transient interactions between multiple proteins. The isolation of intact protein complexes is essential to understanding biochemical processes and an important prerequisite for identifying new drug targets and biomarkers. However, low-affinity interactions are often difficult to detect. Here, we use a newly described method called immiscible filtration assisted by surface tension (IFAST) to isolate proteins under defined binding conditions. This method, which gives a near-instantaneous isolation, enables significantly higher recovery of transient complexes compared to current wash-based protocols, which require reequilibration at each of several wash steps, resulting in protein loss. The method moves proteins, or protein complexes, captured on a solid phase through one or more immiscible-phase barriers that efficiently exclude the passage of nonspecific material in a single operation. We use a previously described polyol-responsive monoclonal antibody to investigate the potential of this new method to study protein binding. In addition, difficult-to-isolate complexes involving the biologically and clinically important Wnt signaling pathway were isolated. We anticipate that this simple, rapid method to isolate intact, transient complexes will enable the discoveries of new signaling pathways, biomarkers, and drug targets.     

External signal–mediated polarized growth in fungi

As the majority of fungi are nonmotile, polarized growth in response to an external signal enables them to search for nutrients and mating partners, and hence is crucial for survival and proliferation. Although the mechanisms underlying polarization in response to external signals has commonalities with polarization during mitotic division, during budding, and fission growth, the importance of diverse feedback loops regulating external signal–mediated polarized growth is likely to be distinct and uniquely adapted to a dynamic environment. Here, we highlight recent advances in our understanding of the mechanisms that are crucial for polarity in response to external signals in fungi, with particular focus on the roles of membrane traffic, small GTPases, and lipids, as well as the interplay between cell shape and cell growth.     

Gene regulation and signal transduction in the ICE–CBF–COR signaling pathway during cold stress in plants

Low temperature is an abiotic stress that adversely affects the growth and production of plants. Resistance and adaptation of plants to cold stress is dependent upon the activation of molecular networks and pathways involved in signal transduction and the regulation of cold-stress related genes. Because it has numerous and complex genes, regulation factors, and pathways, research on the ICE–CBF–COR signaling pathway is the most studied and detailed, which is thought to be rather important for cold resistance of plants. In this review, we focus on the function of each member, interrelation among members, and the influence of manipulators and repressors in the ICE–CBF–COR pathway. In addition, regulation and signal transduction concerning plant hormones, circadian clock, and light are discussed. The studies presented provide a detailed picture of the ICE–CBF–COR pathway.     

Sensitive detection of C-reactive protein in serum by immunoprecipitation–microchip capillary gel electrophoresis

Sepsis represents a significant cause of mortality in intensive care units. Early diagnosis of sepsis is essential to increase the survival rate of patients. Among others, C-reactive protein (CRP) is commonly used as a sepsis marker. In this work we introduce immune precipitation combined with microchip capillary gel electrophoresis (IP–MCGE) for the detection and quantification of CRP in serum samples. First high-abundance proteins (HSA, IgG) are removed from serum samples using affinity spin cartridges, and then the remaining proteins are labeled with a fluorescence dye and incubated with an anti-CRP antibody, and the antigen/antibody complex is precipitated with protein G-coated magnetic beads. After precipitation the complex is eluted from the beads and loaded onto the MCGE system. CRP could be reliably detected and quantified, with a detection limit of 25 ng/μl in serum samples and 126 pg/μl in matrix-free samples. The overall sensitivity (LOQ = 75 ng/μl, R² = 0.9668) of the method is lower than that of some specially developed methods (e.g., immune radiometric assay) but is comparable to those of clinically accepted ELISA methods. The straightforward sample preparation (not prone to mistakes), reduced sample and reagent volumes (including the antibodies), and high throughput (10 samples/3 h) are advantages and therefore IP–MCGE bears potential for point-of-care diagnosis.     

Determination of very-long-chain fatty acids in serum by gas chromatography–nitrogen–phosphorus detection following cyanomethylation

A sensitive method for very-long-chain fatty acid analysis was developed by gas chromatography–nitrogen–phosphorus detection by using cyanomethyl derivatization. Bromoacetonitrile as alkylating reagent was used to improve nitrogen phosphorus detection detectability of compounds containing non-nitrogen. The carboxyl group of very-long-chain fatty acid was alkylated to cyanomethyl esters. Reaction conditions were 40 min at 60°C under potassium carbonate base. Heptacosanoic acid was used as an internal standard and hexane was used as a solvent of extraction. The extraction yield was 82.8% or more, relative standard deviation of the precision test was 8.3 % or more and the result of linearity test showed a good correlation coefficient of r²=0.999 in the range of 0.1–50 μg/ml. The quantification limits were 10 ng/ml when 0.5 ml of serum was used. The present method proved simple, rapid, inexpensive and resistant to contaminants. When it was applied to serum samples taken from patients with X-linked adrenoleukodystrophy which is a hereditary X-linked disorder characterized by progressive demyelination and adrenal insufficiency during childhood, relative increase of the concentration of hexacosanoic acid and the concentration ratios of hexacosanoic, lignoceric to behenic acid was observed in comparison with control samples.     

Periodic coupling strength-dependent multiple coherence resonance by time delay in Newman–Watts neuronal networks

Recently, multiple coherence resonance induced by time delay has been observed in neuronal networks with constant coupling strength. In this paper, by employing Newman–Watts Hodgkin–Huxley neuron networks with time-periodic coupling strength, we study how the temporal coherence of spiking behavior and coherence resonance by time delay change when the frequency of periodic coupling strength is varied. It is found that delay induced coherence resonance is dependent on periodic coupling strength and increases when the frequency of periodic coupling strength increases. Periodic coupling strength can also induce multiple coherence resonance, and the coherence resonance occurs when the frequency of periodic coupling strength is approximately multiple of the spiking frequency. These results show that for periodic coupling strength time delay can more frequently optimize the temporal coherence of spiking activity, and periodic coupling strength can repetitively optimize the temporal coherence of spiking activity as well. Frequency locking may be the mechanism for multiple coherence resonance induced by periodic coupling strength. These findings imply that periodic coupling strength is more efficient for enhancing the temporal coherence of spiking activity of neuronal networks, and thus it could play a more important role in improving the time precision of information processing and transmission in neural networks.     

Conformational changes of the histidine ATP-binding cassette transporter studied by double electron–electron resonance spectroscopy

The conformational dynamics of the histidine ABC transporter HisQMP₂ from Salmonella enterica serovar Typhimurium, reconstituted into liposomes, is studied by site-directed spin labeling and double electron–electron resonance spectroscopy in the absence of nucleotides, in the ATP-bound, and in the post-hydrolysis state. The results show that the inter-dimer distances as measured between the Q-loops of HisP₂ in the intact transporter resemble those determined for the maltose transporter in all three states of the hydrolysis cycle. Only in the presence of liganded HisJ the closed conformation of the nucleotide binding sites is achieved revealing the transmembrane communication of the presence of substrate. Two conformational states can be distinguished for the periplasmic moiety of HisQMP₂ as detected by differences in distributions of interspin distances between positions 86 and 96 or 104 and 197. The observed conformational changes are correlated to proposed open, semi-open and closed conformations of the nucleotide binding domains HisP₂. Our results are in line with a rearrangement of transmembrane helices 4 and 4′ of HisQM during the closed to the semi-open transition of HisP₂ driven by the reorientation of the coupled helices 3a and 3b to occur upon hydrolysis.     

Shaker-like potassium channels in Populus, regulated by the CBL–CIPK signal transduction pathway, increase tolerance to low-K+ stress

Shaker-like potassium channels in plants play an important role in potassium absorption and transport. Here, we characterized 11 genes encoding shaker-like channels from Populus trichocarpa. Furthermore, two homologs from this family were isolated from Populus euphratica and named PeKC1 and PeKC2. Subcellular localization analysis of them in Nicotiana benthamiana revealed that they are located in the cell membrane. Yeast two-hybrid assays showed that they not only interacted strongly with PeCIPK24, a homolog of AtCIPK23, but also interacted with several other CIPK members, including PeCIPK10 and PeCIPK17. To further analyze their function, we over-expressed PeKC1 or PeKC2 in akt1 mutant, the results show that the transgenic plant can recover the mutant phonotype sensitive to low-K⁺ stress. This means PeKC1 or PeKC2 can complement the function of AKT1 in akt1 mutant, involved in the CBL1-CIPK23 signal transduction pathway and play an important role under low-K⁺ stress.     

Positive φ-angles in proteins by nuclear magnetic resonance spectroscopy

Summary Non-glycine residues with positive -angles have been identified in four proteins, barley serine proteinase inhibitor CI-2, bacterial ribonuclease (barnase) ofBacillus amyloliquefaciens, hen egg white lysozyme and a basic protein from barley seed (barwin) by use of nuclear magnetic resonance spectroscopy. By accurate measurements of the coupling constant and integration of the nuclear Overhauser H^N-H cross peak, positive -angles could be determined reliably to 60°±30°, in full agreement with the crystal structures for lysozyme, barnase and serine proteinase inhibitor CI-2. The work emphasizes that positive -angles can also occur in non-glycine residues and in the four proteins, positive -angles have been observed for the residue types aspartic acid, asparagine, arginine, serine, glutamine, histidine, tyrosine, tryptophan and phenylalanine. The measured coupling constants and the intensity of the intraresidue H^N-H NOEs agree well with the solution structures of three of the proteins, using the existing parametrization of the Karplus curve (Pardi, A., Billeter, M. and Wüthrich, K. (1984)J. Mol. Biol.,180, 741–751; Ludvigsen, S., Andersen, K.V. and Poulsen, F.M. (1991)J. Mol. Biol.,217, 731–736).