Activity pattern detection in electroneurographic and electromyogram signals through a heteroscedastic change-point method

In this work, we propose a heteroscedastic method in the detection of activity patterns of electroneurographic and electromyogram signals involved in rhythmic activities of nerves and muscles, respectively. The electric behavior observed in such signals is characterized by phases of activity and silence. The beginning and the length of electrically active and electrically silent phases in a signal allow us to quantitatively analyze the changes and the effects on a rhythmic activity produced by experimental changes. In order to distinguish between these two phases, signals are assumed to be a sample of a time-dependent, normally distributed random variable with non-constant variance, and that the determination of the variance at each point allows us to determine in which phase is the signal. The parameters of the model are determined by means of an iterative process which maximizes the log-likelihood under the proposed model. Moreover, we apply our method to the determination of the activity phases and silence phases in sequences of experimental and synthetic electroneurographic and electromyogram signals. The results obtained with synthetic data show that the method performs well in the determination of these activity patterns. Finally, the study of particular signals simulated under a generalized autoregressive conditional heteroscedasticity model suggests the robustness of the method with respect to the assumption of independence.     

Use of the lateral line and tactile senses in feeding in four antarctic nototheniid fishes

Synopsis Fishes of the family Nototheniidae (Pisces: Perciformes) dominate antarctic fish communities and have radiated to fill diverse niches. The most southern species must operate under an extended austral night and under thick sea ice, yet have eyes more typical of shallow coastal fishes. In winter, the eyes are probably useless, except for detecting bioluminescence. I compared the responses of four species to hydromechanical and tactile signals: two benthivores,Trematomus bernacchii andT. pennellii, a benthic planktivore,T. nicolai, andPagothenia borchgrevinki, which feeds near the ice undersurface and within ice cracks. The planktivores have dorsal mouths, with eyes oriented dorsally or laterally (Pagothenia); their lateral line canals and receptor organs are larger dorsally. The benthivores have more ventrally oriented mouths and eyes. All species responded to hydromechanical cues to the head, but only the two benthivores responded to trunk hydromechanical stimuli or tactile stimuli to the ventral trunk or pelvic fins. Possibly responses to plankton along the trunk are of little use if a reorientation washes pelagic prey away. In responding to trunk stimuli,T. bernacchii reorients its head to the target in two stages by slowly pivoting on its pelvic fins. In contrast,T. pennellii reorients in a single quick flip. It is argued that, becauseT. bernacchii has wider canals thanT. pennellii, it must move more slowly to reduce self-generated noise. It is likely that further studies of winter diet and prey behavior may reveal the relative advantages of the two repositioning styles.     

Autocorrelation function and power spectrum of two-state random processes used in neurite guidance.

During development neurons extend and retract cytoskeletal structures, chiefly microtubules and filopodia, to process informational cues from the extracellular environment and thereby guide growth cone migration toward an appropriate synaptic partner. This cytoskeleton-based exploration is achieved by stochastic switching, with microtubules and filopodia alternating between growing and shortening phases apparently at random. If stabilizing signals are not detected during the growth phase, then the structures switch to a shortening state, from which they can again return to a growth phase, and so forth. A useful means of characterizing these stochastic processes in a model-independent way is by autocorrelation and spectral analysis. Previously, we compared experiment to theory by performing Monte Carlo simulations and computing the autocorrelation function and power spectrum from the simulated dynamics, an approach that is computationally intensive and requires recalculation whenever model parameters are changed. Here we present analytical expressions for the autocorrelation function and power spectrum, which compactly characterize microtubule and filopodial dynamics based on the stochastic, two-state model. The model assumes that the phase times are of variable duration and gamma-distributed, consistent with experimental evidence for microtubules assembled in vitro from purified tubulin. The analytical expressions permit the precise quantitative characterization of changes in microtubule and filopodial searching behavior corresponding to changes in the shape of the gamma distribution.     

Oscillator model reduction preserving the phase response: application to the circadian clock

Mathematical model reduction is a long-standing technique used both to gain insight into model subprocesses and to reduce the computational costs of simulation and analysis. A reduced model must retain essential features of the full model, which, traditionally, have been the trajectories of certain state variables. For biological clocks, timing, or phase, characteristics must be preserved. A key performance criterion for a clock is the ability to adjust its phase correctly in response to external signals. We present a novel model reduction technique that removes components from a single-oscillator clock model and discover that four feedback loops are redundant with respect to its phase response behavior. Using a coupled multioscillator model of a circadian clock, we demonstrate that by preserving the phase response behavior of a single oscillator, we preserve timing behavior at the multioscillator level.     

Force sensing and generation in cell phases: analyses of complex functions.

Cellular morphology is determined by motility, force sensing, and force generation that must be finely controlled in a dynamic fashion. Contractile and extensile functions are integrated with the overall cytoskeleton, including linkages from the cytoplasmic cytoskeleton to the extracellular matrix and other cells by force sensing. During development, as cells differentiate, variations in protein expression levels result in morphological changes. There are two major explanations for motile behavior: either cellular motility depends in a continuous fashion on cell composition or it exhibits phases wherein only a few protein modules are activated locally for a given time. Indeed, in support of the latter model, the quantification of cell spreading and other motile activities shows multiple distinct modes of behavior, which we term "phases" because there exist abrupt transitions between them. Cells in suspension have a basal level of motility that enables them to probe their immediate environment. After contacting a matrix-coated surface, they rapidly transition to an activated spreading phase. After the development of a significant contact area, the cells contract repeatedly to determine the rigidity of the substrate and then develop force on matrix contacts. When cells are fully spread, extension activity is significantly decreased and focal complexes start to assemble near the cell periphery. For each of these phases, there are significant differences in protein activities, which correspond to differences in function. Thus overall morphological change of a tissue is driven by chemical signals and force-dependent activation of one or more motile phases in limited cell regions for defined periods.     

Kinetic analysis of the nicking and hairpin formation steps in V(D)J recombination

The complete cleavage phase of V(D)J recombination includes four phases: binding of the active RAG complexes to the 12- or 23-signals, nicking of the signals, synapsis of the two signals, and hairpin formation at both signals concurrently. We have done time courses for the complete cleavage phase of the V(D)J recombination reaction and quantitated the amount of active RAG enzyme. We have also formulated a kinetic model for the binding, nicking, synapsis, and hairpin formation phases. We have utilized free solution enzymatic measurements for the binding and nicking phases as we do mathematical simulations of the kinetic model. This permits iteration of rate constants for the synapsis and hairpin formation phases until the model fits the observed overall cleavage time course. This process yields a rate constant for the hairpin formation that is 0.004 min(-1), which corresponds to an average catalytic cycle time of 250 min. This value is exceedingly close to a measured value of this constant that relied on wash-out of an inhibitory cofactor. The agreement indicates that this is likely to be the rate of the hairpin step over a wide range of range of conditions and irrespective of the DNA sequence of the V, D or J coding end located adjacent to the signal. These findings indicate that, under optimal in vitro conditions, the core RAG proteins carry out nicking at a rate which is nearly 150-fold faster than hairpin formation. The physiologic implications of this and other kinetic inferences of these time courses are discussed.     

Lipid dependence of membrane anchoring properties and snorkeling behavior of aromatic and charged residues in transmembrane peptides

31P NMR spectroscopy was used to investigate the effects of transmembrane alpha-helical peptides with different flanking residues on the phase behavior of phosphatidylethanolamine and phosphatidylethanolamine/phosphatidylglycerol (molar ratio 7:3) model membranes. It was found that tryptophan-flanked (WALP) peptides and lysine-flanked (KALP) peptides both promote formation of nonlamellar phases in these lipid systems in a mismatch-dependent manner. Based on this mismatch dependence, it was concluded that the effective hydrophobic length of KALP peptides is considerably shorter than that of the corresponding WALP peptides. Peptides with other positively charged residues showed very similar effects as KALP. The results suggest that the peptides have a well-defined effective hydrophobic length, which is different for charged and aromatic flanking residues, but which is independent of the precise chemical nature of the side chain. Strikingly, the effective length of KALP peptides in the lipid systems investigated here is much smaller than that previously found for the same peptides in phosphatidylcholine. This suggests that snorkeling of lysine side chains, as proposed to occur in phosphatidylcholine, does not occur in lipid systems that are prone to form nonlamellar phases by themselves. This suggestion was supported by using peptides with shortened lysine side chains and by investigating the effects of mixtures of WALP and KALP peptides. The lipid dependency of the snorkeling behavior is explained by considering the free energy cost of snorkeling in relation to the free energy cost of the formation of nonlamellar phases.     

Polymorphic phase behavior of lysophosphatidylethanolamine dispersions. A thermodynamic and spectroscopic characterization.

We have investigated the phase behavior of aqueous dispersions of a series of synthetic lysophosphatidylethanolamines as a function of the acyl chain length. Lysophosphatidylethanolamines exhibit phase polymorphism encompassing a well-ordered crystalline phase which may arise either from a metastable interdigitated lamellar gel phase or a metastable micellar phase. The time course of interconversion between these various phases have been outlined by observing the low temperature incubation time dependence of the calorimetric thermograms. We have determined differences in structure of these phases by Raman spectroscopy and 31P nuclear magnetic resonance spectroscopy. It appears that a principal contribution to this polymorphic phase behavior lies in the nature of headgroup hydration and headgroup-headgroup interactions.     

Manuo-ocular coordination in target tracking. II. Comparing the model with human behavior

Several studies have shown that humans track a moving visual target with their eyes better if the movement of this target is directly controlled by the observer's hand. The improvement in performance has been attributed to coordination control between the arm motor system and the smooth pursuit (SP) system. In such a task, the SP system shows characteristics that differ from those observed during eye-alone tracking: latency (between the target-arm and the eye motion onsets) is shorter, maximum SP velocity is higher and the maximum target motion frequency at which the SP can function effectively is also higher. The aim of this article is to qualitatively evaluate the behavior of a dynamical model simulating the oculomotor system and the arm motor system when both are involved in tracking visual targets. The evaluation is essentially based on a comparison of the behavior of the model with the behavior of human subjects tracking visual targets under different conditions. The model has been introduced and quantitatively evaluated in a companion paper. The model is based on an exchange of internal information between the two sensorimotor systems, mediated by sensory signals (vision, arm muscle proprioception) and motor signals (arm motor command copy). The exchange is achieved by a specialized structure of the central nervous system, previously identified as a part of the cerebellum. Computer simulation of the model yielded results that fit the behavior of human subjects observed during previously reported experiments, both qualitatively and quantitatively. The parallelism between physiology and human behavior on the one hand, and structure and simulation of the model on the other hand, is discussed. Received: 6 March 1997 / Accepted in revised form: 15 July 1997     

The phase behavior of cationic lipid-DNA complexes

We present a theoretical analysis of the phase behavior of solutions containing DNA, cationic lipids, and nonionic (helper) lipids. Our model allows for five possible structures, treated as incompressible macroscopic phases: two lipid-DNA composite (lipoplex) phases, namely, the lamellar (L(alpha)(C)) and hexagonal (H(II)(C)) complexes; two binary (cationic/neutral) lipid phases, that is, the bilayer (L(alpha)) and inverse-hexagonal (H(II)) structures, and uncomplexed DNA. The free energy of the four lipid-containing phases is expressed as a sum of composition-dependent electrostatic, elastic, and mixing terms. The electrostatic free energies of all phases are calculated based on Poisson-Boltzmann theory. The phase diagram of the system is evaluated by minimizing the total free energy of the three-component mixture with respect to all the compositional degrees of freedom. We show that the phase behavior, in particular the preferred lipid-DNA complex geometry, is governed by a subtle interplay between the electrostatic, elastic, and mixing terms, which depend, in turn, on the lipid composition and lipid/DNA ratio. Detailed calculations are presented for three prototypical systems, exhibiting markedly different phase behaviors. The simplest mixture corresponds to a rigid planar membrane as the lipid source, in which case, only lamellar complexes appear in solution. When the membranes are "soft" (i.e., low bending modulus) the system exhibits the formation of both lamellar and hexagonal complexes, sometimes coexisting with each other, and with pure lipid or DNA phases. The last system corresponds to a lipid mixture involving helper lipids with strong propensity toward the inverse-hexagonal phase. Here, again, the phase diagram is rather complex, revealing a multitude of phase transitions and coexistences. Lamellar and hexagonal complexes appear, sometimes together, in different regions of the phase diagram.     

A nonlinear model for transient responses from light-adapted wolf spider eyes

A quantitative model is proposed to test the hypothesis that the dynamics of nonlinearities in retinal action potentials from light-adapted wolf spider eyes may be due to delayed asymmetries in responses of the visual cells. For purposes of calculation, these delayed asymmetries are generated in an analogue by a time-variant resistance. It is first shown that for small incremental stimuli, the linear behavior of such a resistance describes peaking and low frequency phase lead in frequency responses of the eye to sinusoidal modulations of background illumination. It also describes the overshoots in linear step responses. It is next shown that the analogue accounts for nonlinear transient and short term DC responses to large positive and negative step stimuli and for the variations in these responses with changes in degree of light adaptation. Finally, a physiological model is proposed in which the delayed asymmetries in response are attributed to delayed rectification by the visual cell membrane. In this model, cascaded chemical reactions may serve to transduce visual stimuli into membrane resistance changes.     

Characterization of depression-like behavior in prenatally stressed female rats during ovary cycle

The aim of the present work was a comparative analysis of dynamics of depression-like behavior in prenatally stressed and non-prenatally stressed female rats in the key phases of the ovary cycle. It was found that non-stressed female rats demonstrated high level of depression-like behavior in proestrous phase as compared to the diestrous phase, whereas these rats showed low level of depression-like behavior in estrous phase in Porsolt's test. On the contrary, there were no significant differences in extent of depression-like behavior between prenatally stressed rats in the diestrous and proestrous, although in the phase of estrous in these animals an increase in level of depression-like behavior was noted. Thus, the results of this study indicated pronounced effects of prenatal stress on the character of depression-like behavior of females in different phases of ovary cycle. This study revealed leveling and reversed action of prenatal stress on depression-like behavior in key phases of sexual cycle in female rats.     

Physiological analysis of cercarial behavior.

The behavior of trematode cercariae was made accessible to physiological analyses by splitting the continuous flow of behavior into separate units of behavior patterns. Such phases include active, passive, and resting phases in the intermittent swimming mode, attachment to the host, remaining on the host, directed creeping to suitable entry sites, and penetration phases including penetration movements, tail shedding, tegument transformation, and secretion of enzymes. Each of these phases may be stimulated by separate environmental and host signals. The pattern of the responses and the chemical, thermal, mechanical, and visual stimuli have been described in some detail but only a few studies have dealt with the question of how these responses are coordinated by receptors and nervous systems. Highly specific and sensitive chemoreceptors for host signals such as carbon dioxide, L-arginine, fatty acids, and glycoproteins have been defined from cercarial behavior, but they have not yet been allocated to morphological structures. Analyses of cercarial behavior of 6 schistosomatid and 4 fish-infecting species revealed that the individual parasite species show different behavioral patterns and respond to very different host signals, even though they infect congeneric hosts. The adaptive benefits of such behavioral diversity and complexity still are to be elucidated.     

General morphology of the brain of the blind cave beetle,Neaphaenops tellkampfii Erichson (Coleoptera : Carabidae)

Neaphaenops tellkampfii (Coleoptera : Carabidae) was collected from Cartmill Cave located in Hart County, Kentucky, U.S.A. This is a cave insect with complete absence of external evidence of eyes or ocelli. The brain of N. tellkampfii has been studied at the light microscope level using Rowell's (1963) silver staining method. Particular attention has been paid to the protocerebrum. One of the notable features of the brain is the dominance of the corpora pedunculata. The corpora pedunculata consists of a calyx, with 3 groups of fibers originating from the Kenyon cells. The stalk is arranged into 2 distinct layers with alpha and beta lobes. The central complex is located anterio-medially beneath the pons cerebralis. It consists of central and ellipsoid bodies and a single ventral tubercle. The ellipsoid body is connected to the beta lobes by a unique chiasmatic fiber tract. The pons cerebralis appears to be formed by 3 distinct groups of globuli cells sending fibers into the pons. The accessory lobes are situated posterio-laterally. The antennal lobes are located posterio-ventrally. Two tubercles were observed lateral to the protocerebrum which may be vestigial optic tubercles. There is no evidence of typical optic lobes or associated fiber tracts. Fiber connections were observed between the calyx and pons cerebralis, the calyx and central body, and also between the calyx and antennal lobe. Two fiber tracts not previously described were observed extending obliquely from the accessory lobe to the beta lobe and protocerebrum.