The dynamics of long term exploration in the rat

Rat exploratory behavior consists of regular excursions into the environment from a preferred place termed a home base. A phase plane representation of excursions reveals a geometrical pattern that changes during exploration in both shape and size. We first show that with time and repeated exposures to the same large environment there is a gradual increase in the length of excursions; each rat has its own characteristic length of excursions; but all rats share a similar rate of excursion growth. As in our experimental setup the rats perform increasingly longer paths from one location, while locomoting back and forth along the walls of the arena, exposure is more extensive at the proximal part of the route, and less at the distal part. We consequently show that the rat's velocity pattern changes concurrently with the increase in excursion length, and in correlation with the level of exposure (familiarity) to places. The primitive velocity pattern consists of slow progression while moving away from base and fast progression while returning to it. During exposure the asymmetry in velocity is inverted. The inversion spreads across successive excursions from the home base outwards. The rate of spread of this inversion is higher than the rate of increase in excursion length, and is similar across rats. Because it spreads more rapidly than the increase in excursion length, the global shape of the excursion trajectory changes. The dynamics of excursion shape share similar properties with the dynamics of excursion length. Both might reflect the same intrinsic constraints on the amount of novelty that a rat can handle per excursion. Received: 16 August 1996 / Accepted in revised form: 20 March 1998     

Dpp gradient formation in the Drosophila wing imaginal disc

The secreted signaling protein Dpp acts as a morphogen to pattern the anterior-posterior axis of the Drosophila wing. Dpp activity is required in all cells of the developing wing imaginal disc, but the ligand gradient that supports this activity has not been characterized. Here we make use of a biologically active form of Dpp tagged with GFP to examine the ligand gradient. Dpp-GFP forms an unstable extracellular gradient that spreads rapidly in the wing disc. The activity gradient visualized by MAD phosphorylation differs in shape from the ligand gradient. The pMAD gradient adjusted to compartment size when this was experimentally altered. These observations suggest that the Dpp activity gradient may be shaped at the level of receptor activation.     

Propagation properties of vasomotion at terminal arterioles and precapillaries in the rabbit mesentery

A vasomotion activity in the mesentery of anesthetized rabbits were studied by simultaneous measurements of inside diameters at multiple sites in arterioles, precapillaries and their bifurcations. A frame-by-frame diameter determination technique was used with a microcomputer-assisted laser video disk recorder and video-image analysis system. Simultaneous intensity profiles across microvessels were continuously obtained. Applying an automatic wall surface tracer and a graphic editor to construct temporal sequences of intensity profiles, we obtained digitized data of inside diameters of microvessels, and implemented cross-correlation analysis between data sets to calculate phase differences of vasomotion at separated sites. The present analysis of the propagation of vasomotion showed that the vasomotion originated from the orifice of precapillaries at the bifurcations, spreading downstream in the precapillary. The vasomotion wave spreads both upstream and downstream along single arterioles from various origins of the vasomotion activity. The propagation velocity of vasomotion was 0.17 +/- 0.03 mm/sec (n = 19), and it became significantly slower through the branching points than along the arterioles. It is suggested that the vasomotion in terminal arterioles and precapillaries may spread through some mechanical transmission factors.     

An electrophysiological study of mechanisms controlling polyp retraction in colonies of the scleractinian coral Goniopora lobata.

1. Electrical or mechanical stimulation of Goniopora lobata produces coordinated retraction of polyps in the colony. With repetitive stimulation, the response spreads in linear, radial increments which become successively smaller with each stimulus. 2. Electrical activity recorded from these colonies is interpreted as originating in a conduction system responsible for effecting the colonial retraction response. The electrical activity spreads incrementally through the colony in a similar manner to the behavioural response. 3. Various hypotheses have been proposed to account for such a spread of electrical acitvity. Of these, only interneural facilitation is of appreciable importance to Goniopora. 4. Temporary termination of a pathway, by the passage of an impulse through it, was found and interpreted as being an additional and important property of the colonial conduction system.     

Spreading of liposomes at the air/water interface

Two types of film structure are formed when liposomes are spread at the air/water interface. At zero surface pressure, there is a slow transformation of the closed bilayered structure into a lipid monolayer. The internal content of the liposomes is released into the aqueous subphase. In contrast, when multilamellar liposomes are spread against a surface pressure, they retain their internal content at the air/water interface by forming multilayered structures. Among the liposomes which dipped through the interface an important fraction loses its internal content. During the spreading process at zero surface pressure, it seems that the outer layer of the liposome spreads with a better yield as compared with the inner layer. It is possible to use this spreading technique to determine the asymmetrical distribution of lipids across bilayers.     

Synaptonemal complex analysis of hybrid cattle. I. Pachytene substaging and the normal full bloods

Meiotic chromosome pairing abnormalities in full-blood and hybrid Bos taurus and B. indicus cattle have been surveyed by electron microscopy of pachytene synaptonemal complex spreads. In this paper the full-blood spreads are described in detail, including the use of XY and nucleolar morphology and other measured parameters for pachytene substaging. Pairing abnormalities were observed in up to 9% of the full-blood spreads. Most of these pairing abnormalities (83%) occurred in early-pachytene spreads, suggesting that the mechanism of synaptic adjustment may operate in cattle.     

Coupling of the respiratory rhythm in fish with activity in hypobranchial nerves and with heartbeat

Fish have a central respiratory pattern generator (CRPG) in the brain stem that initiates activity in a series of cranial nerves innervating respiratory muscles. These nerves burst sequentially in the order of their rostrocaudal distribution in the central nervous system. When respiratory drive is high, this activity spreads caudally to occipital and anterior spinal neurons that project via the hypobranchial nerves to stimulate hypaxial muscles, causing active jaw abduction. The CRPG may also recruit the heart. Fish, like mammals, show respiratory components in the intrinsic variability of heart rate (HRV). Cardiorespiratory synchrony in the dogfish is driven by bursting activity in the cardiac branches of the vagus nerve, which emanates from preganglionic neurons in the dorsal vagal motor nucleus. A respiratory component in HRV is difficult to discriminate in other species, requiring the use of power spectral analysis and the subsequent elimination of aliased components.     

Patterns of intercostal muscle activity in humans

Coordination of activity of inspiratory intercostal muscles in conscious human subjects was studied by means of an array of electromyograph (EMG) electrodes. Bipolar fine wire electrodes were placed in the second and fourth parasternal intercostal muscles and in two or three external intercostal muscles in the midaxillary line from the fourth to eighth intercostal spaces. Subjects breathed quietly or rebreathed from a bag containing 8% CO2 in O2 in both supine and upright postures. Respiration was monitored by means of flow, volume, and separate rib cage and abdominal volumes. Onset of EMG activity in each breath was found near the beginning of inspiration in the uppermost intercostal spaces but progressively later in inspiration in lower spaces, indicating that activity spreads downward across the rib cage through inspiration. At higher ventilation stimulated by CO2, activity spread further and faster downward. In voluntary deep breathing, external intercostal muscles tended to be recruited earlier in inspiration than in CO2-stimulated breathing. The change from supine to sitting resulted in small and inconsistent changes. There was no lung volume or rib cage volume threshold for appearance of EMG activity in any of the spaces.     

Localization of single- and low-copy sequences on tomato synaptonemal complex spreads using fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) is a powerful means by which single- and low-copy DNA sequences can be localized on chromosomes. Compared to the mitotic metaphase chromosomes that are normally used in FISH, synaptonemal complex (SC) spreads (hypotonically spread pachytene chromosomes) have several advantages. SC spreads (1) are comparatively free of debris that can interfere with probe penetration, (2) have relatively decondensed chromatin that is highly accessible to probes, and (3) are about ten times longer than their metaphase counterparts, which permits FISH mapping at higher resolution. To investigate the use of plant SC spreads as substrates for single-copy FISH, we probed spreads of tomato SCs with two single-copy sequences and one low-copy sequence (ca. 14 kb each) that are associated with restriction fragment length polymorphism (RFLP) markers on SC 11. Individual SCs were identified on the basis of relative length, arm ratio, and differential staining patterns after combined propidium iodide (PI) and 4', 6-diamidino-2-phenylindole (DAPI) staining. In this first report of single-copy FISH to SC spreads, the probe sequences were unambiguously mapped on the long arm of tomato SC 11. Coupled with data from earlier studies, we determined the distance in micrometers, the number of base pairs, and the rates of crossing over between these three FISH markers. We also observed that the order of two of the FISH markers is reversed in relation to their order on the molecular linkage map. SC-FISH mapping permits superimposition of markers from molecular linkage maps directly on pachytene chromosomes and thereby contributes to our understanding of the relationship between chromosome structure, gene activity, and recombination.     

Physiology of interdigestive motor activity in man

Aim of this work has been to investigate the pattern of interdigestive motility from the esophagus to the duodenum. Six human subjects have been studied by means of a manometric probe. The results are very similar to those described elsewhere, and show that a cyclic motor activity spreads down from the esophagus to the duodenum and that a district control of gastrointestinal motility exists.     

Zebrafish Dynamin is required for maintenance of enveloping layer integrity and the progression of epiboly

Epiboly, the first morphogenetic cell movement that occurs in the zebrafish embryo, is the process by which the blastoderm thins and spreads to engulf the yolk cell. This process requires the concerted actions of the deep cells, the enveloping layer (EVL) and the extra-embryonic yolk syncytial layer (YSL). The EVL is mechanically coupled to the YSL which acts as an epiboly motor, generating the force necessary to draw the blastoderm towards the vegetal pole though actomyosin flow and contraction of the actomyosin ring. However, it has been proposed that the endocytic removal of yolk cell membrane just ahead of the advancing blastoderm may also play a role. To assess the contribution of yolk cell endocytosis in driving epiboly movements, we used a combination of drug- and dominant-negative-based approaches to inhibit Dynamin, a large GTPase with a well-characterized role in vesicle scission. We show that Dynamin-dependent endocytosis in the yolk cell is dispensable for epiboly of the blastoderm. However, global inhibition of Dynamin function revealed that Dynamin plays a fundamental role within the blastoderm during epiboly, where it maintains epithelial integrity and the transmission of tension across the EVL. The epithelial defects were associated with disrupted tight junctions and a striking reduction of cortically localized phosphorylated ezrin/radixin/moesin (P-ERM), key regulators of epithelial integrity in other systems. Furthermore, we show that Dynamin maintains EVL and promotes epiboly progression by antagonizing Rho A activity.     

Within-session modulation of timed anticipatory responding: When to start responding

The peak procedure is widely used in the study of interval timing with animals. Multiple timing measures can be derived from peak responding. These measures are typically presented as averages across many trials based on the implicit assumption that peak responding is stable throughout the session. We tested this assumption by examining whether peak responding changed over the course of the session in 45 mice that were trained on a fixed-interval 30-s schedule. All common measures of peak responding, except stop times, changed over the course of the session: start times increased, response rates and spreads decreased, and, although less reliably, peak times also shifted rightward. These results are congruent with a motivational interpretation, whereby increased satiety leads to the observed behavioral signature of within-session modulation of timed anticipatory responding.     

The frequency of high avidity T cells determines the hierarchy of determinant spreading

Autoimmunity often spreads in a predefined pattern during the progression of T cell-mediated autoimmune diseases. This progression has been well described in animal models and in man, but the basis for this phenomenon is little understood. To gain insight into the factors that determine this spreading hierarchy, we characterized the binding affinity of a panel of beta cell-autoantigenic peptides to I-Ag7, as well as the precursor frequency, functional avidity, and phenotype of the T cells that recognize these peptides in type 1 diabetes-prone nonobese diabetic mice. We observed that autoimmunity gradually spreads from a beta cell determinant, which had the largest precursor pool of high avidity T cells, to beta cell determinants with progressively smaller and lower avidity T cell precursor pools. This correlation between the sequential development of spontaneous T cell autoimmunity and the frequency and avidity of autoantigen-reactive T cells suggests that the extent to which T cells were negatively selected by the self-determinants is the key factor determining the spreading hierarchy.     

Sandwich Embedding of Monolayers of Cells in Epoxy Resin for Ultrathin Sectioning

In this procedure for embedding monolayers of cells, the usual glass slides are replaced by plates of resin 1-1.5 mm thick. Unlike the open-face embedding technique, the present procedure uses only a few drops of unpolymerized resin, which are applied to the fixed and dehydrated cells. During polymerization this small amount of liquid resin spreads across a relative large area, leaves the cells covered by a very thin layer, and permits phase contrast observations through it. Ultrathin sections of a particular cell encircled by a rotary scriber can be obtained by sectioning the resin slide, which has been trimmed and mounted directly in the specimen holder of the ultramicrotome.     

Improved viability of populations with diverse life-history portfolios

A principle shared by both economists and ecologists is that a diversified portfolio spreads risk, but this idea has little empirical support in the field of population biology. We found that population growth rates (recruits per spawner) and life-history diversity as measured by variation in freshwater and ocean residency were negatively correlated across short time periods (one to two generations), but positively correlated at longer time periods, in nine Bristol Bay sockeye salmon populations. Further, the relationship between variation in growth rate and life-history diversity was consistently negative. These findings strongly suggest that life-history diversity can both increase production and buffer population fluctuations, particularly over long time periods. Our findings provide new insights into the importance of biocomplexity beyond spatio-temporal aspects of populations, and suggest that maintaining diverse life-history portfolios of populations may be crucial for their resilience to unfavourable conditions like habitat loss and climate change.     

Spreading ciliary arrest in a mussel gill epithelium: characterization by quick fixation

Spreading ciliary arrest, induced by local laser microinjury, in freshwater mussel (e.g., Elliptio) gill lateral (L) cell cilia, has been characterized by quick fixation with osmium tetroxide, which permits the correlation of known features of the response with structural features of the gill epithelium. Quick fixation reliably preserves the state of the epithelium including the activity state of the L cilia at the moment of fixation. From a disrupted region, the stimulus that triggers arrest spreads outward along an undamaged filament preferentially from L cell to L cell for more than 300 microns to either side of the lesion. In physiological salt solutions transverse spread across the filament via heterologous cells is insufficient to elicit L ciliary arrest on the opposite side of the filament. The spread of arrest is dependent upon the structural integrity of the L epithelium, normally terminates at a boundary between adjacent L cells, and does not spread past a focal break. Arrest occurs asynchronously because cilia in different stroke positions respond to the stimulus with different time courses. The cilia stop in a uniform "hands up" position, i.e., pointing frontally. The arrest response is inhibited by reducing the concentration of extracellular Ca2+ (less than 10(-7) M) or by adding extracellular La3+ (1 mM) or K+ (15 mM). Recovery begins at the margin of a segment of arrested L cilia and spreads back toward the lesion at a constant initial velocity of ca. 60 microns/sec. About 300 microns from the lesion the recovery velocity rapidly falls to ca. 5 microns/sec. Recovery of ciliary beat precedes the recovery of metachronal coordination. Neither spread of the stimulus nor recovery require ciliary beat. The data support the hypothesis that the microinjury-induced arrest is initiated by an injury potential that triggers a graded regenerative depolarization that is propagated electrotonically along the epithelium from L cell to L cell, triggering Ca2+ influx into the axoneme and consequent Ca2+-induced L ciliary arrest as it spreads. A temporary non-linear gradient of intracellular Ca2+ concentration is established along the injured L epithelial tract. As individual cells recover, they lower their intracellular Ca2+ concentration from pCa 5 to pCa 7 in about 10 seconds.     

A continuous assay for foot-and-mouth disease virus 3C protease activity

Foot-and-mouth disease virus is a highly contagious pathogen that spreads rapidly among livestock and is capable of causing widespread agricultural and economic devastation. The virus genome is translated to produce a single polypeptide chain that subsequently is cleaved by viral proteases into mature protein products, with one protease, 3C(pro), carrying out the majority of the cleavages. The highly conserved nature of this protease across different viral strains and its crucial role in viral maturation and replication make it a very desirable target for inhibitor design. However, the lack of a convenient and high-throughput assay has been a hindrance in the characterization of potential inhibitors. In this article, we report the development of a continuous assay with potential for high throughput using fluorescence resonance energy transfer-based peptide substrates. Several peptide substrates containing the 3C-specific cleavage site were synthesized, varying both the positions and separation of the fluorescent donor and quencher groups. The best substrate, with a specificity constant k(cat)/K(M) of 57.6+/-2.0M(-1) s(-1), was used in inhibition assays to further characterize the protease's activity against a range of commercially available inhibitors. The inhibition profile of the enzyme showed characteristics of both cysteine and serine proteases, with the chymotrypsin inhibitor TPCK giving stoichiometric inhibition of the enzyme and allowing active site titration of the 3C(pro).     

Determination of embryonic polarity in a regulative system: evidence for endogenous inhibitors acting sequentially during primitive streak formation in the chick embryo

Avian embryos have a remarkable capacity to regulate: when a pre-primitive streak stage embryo is cut into fragments, each fragment can spontaneously initiate formation of a complete embryonic axis. We investigate the signalling pathways that initiate primitive streak formation and the mechanisms that ensure that only a single axis normally forms. As reported previously, an ectopic primitive streak can be induced by misexpression of Vg1 in the marginal zone. We now show that Vg1 induces an inhibitor that travels across the embryo (3 mm distance) in less than 6 hours. We provide evidence that this inhibitor acts early in the cascade of events downstream of Vg1. We also show that FGF signalling is required for primitive streak formation, in cooperation with Nodal and Chordin. We suggest that three sequential inhibitory steps ensure that a single axis develops in the normal embryo: an early inhibitor that spreads throughout the embryo (which can be induced by Vg1), a second inhibition by Cerberus from the underlying hypoblast, and finally a late inhibition from Lefty emitted by the primitive streak itself.     

Forecasting Financial Extremes: A Network Degree Measure of Super-Exponential Growth

Investors in stock market are usually greedy during bull markets and scared during bear markets. The greed or fear spreads across investors quickly. This is known as the herding effect, and often leads to a fast movement of stock prices. During such market regimes, stock prices change at a super-exponential rate and are normally followed by a trend reversal that corrects the previous overreaction. In this paper, we construct an indicator to measure the magnitude of the super-exponential growth of stock prices, by measuring the degree of the price network, generated from the price time series. Twelve major international stock indices have been investigated. Error diagram tests show that this new indicator has strong predictive power for financial extremes, both peaks and troughs. By varying the parameters used to construct the error diagram, we show the predictive power is very robust. The new indicator has a better performance than the LPPL pattern recognition indicator.