Modeling of Noisy Spindle Dynamics Reveals Separable Contributions to Achieving Correct Orientation

The mechanisms by which the mammalian mitotic spindle is guided to a predefined orientation through microtubule-cortex interactions have recently received considerable interest, but there has been no dynamic model that describes spindle movements toward the preferred axis in human cells. Here, we develop a dynamic model based on stochastic activity of cues anisotropically positioned around the cortex of the mitotic cell and we show that the mitotic spindle does not reach equilibrium before chromosome segregation. Our model successfully captures the characteristic experimental behavior of noisy spindle rotation dynamics in human epithelial cells, including a weak underlying bias in the direction of rotation, suppression of motion close to the alignment axis, and the effect of the aspect ratio of the interphase cell shape in defining the final alignment axis. We predict that the force exerted per cue has a value that minimizes the deviation of the spindle from the predefined axis. The model has allowed us to systematically explore the parameter space around experimentally relevant configurations, and predict the mechanistic function of a number of established regulators of spindle orientation, highlighting how physical modeling of a noisy system can lead to functional biological understanding. We provide key insights into measurable parameters in live cells that can help distinguish between mechanisms of microtubule and cortical-cue interactions that jointly control the final orientation of the spindle.     

Animal movements in fire‐prone landscapes

Movement is a trait of fundamental importance in ecosystems subject to frequent disturbances, such as fire‐prone ecosystems. Despite this, the role of movement in facilitating responses to fire has received little attention. Herein, we consider how animal movement interacts with fire history to shape species distributions. We consider how fire affects movement between habitat patches of differing fire histories that occur across a range of spatial and temporal scales, from daily foraging bouts to infrequent dispersal events, and annual migrations. We review animal movements in response to the immediate and abrupt impacts of fire, and the longer‐term successional changes that fires set in train. We discuss how the novel threats of altered fire regimes, landscape fragmentation, and invasive species result in suboptimal movements that drive populations downwards. We then outline the types of data needed to study animal movements in relation to fire and novel threats, to hasten the integration of movement ecology and fire ecology. We conclude by outlining a research agenda for the integration of movement ecology and fire ecology by identifying key research questions that emerge from our synthesis of animal movements in fire‐prone ecosystems.     

Getting into shape: epidermal morphogenesis in Caenorhabditis elegans embryos

The change in shape of the C. elegans embryo from an ovoid ball of cells into a worm-shaped larva is driven by three events within the cells of the hypodermis (epidermis): (1) intercalation of two rows of dorsal cells, (2) enclosure of the ventral surface by hypodermis, and (3) elongation of the embryo. While the behavior of the hypodermal cells involved in each of these processes differs dramatically, it is clear that F-actin and microtubules have essential functions in each of these processes, whereas contraction of actomyosin structures appears to be involved specifically in elongation. Molecular analysis of these processes is revealing components specific to C. elegans as well as components found in other systems. Since C. elegans hypodermal cells demonstrate dramatically different behaviors during intercalation, enclosure and elongation, the study of cytoskeletal dynamics in these processes may reveal both unique and conserved activities during distinct epithelial morphogenetic movements. BioEssays 23:12-23, 2001.     

A role for α-adducin (ADD-1) in nematode and human memory

Identifying molecular mechanisms that underlie learning and memory is one of the major challenges in neuroscience. Taken the advantages of the nematode Caenorhabditis elegans, we investigated α-adducin (add-1) in aversive olfactory associative learning and memory. Loss of add-1 function selectively impaired short- and long-term memory without causing acquisition, sensory, or motor deficits. We showed that α-adducin is required for consolidation of synaptic plasticity, for sustained synaptic increase of AMPA-type glutamate receptor (GLR-1) content and altered GLR-1 turnover dynamics. ADD-1, in a splice-form- and tissue-specific manner, controlled the storage of memories presumably through actin-capping activity. In support of the C. elegans results, genetic variability of the human ADD1 gene was significantly associated with episodic memory performance in healthy young subjects. Finally, human ADD1 expression in nematodes restored loss of C. elegans add-1 gene function. Taken together, our findings support a role for α-adducin in memory from nematodes to humans. Studying the molecular and genetic underpinnings of memory across distinct species may be helpful in the development of novel strategies to treat memory-related diseases.     

An imbalancing act: gap junctions reduce the backward motor circuit activity to bias C. elegans for forward locomotion

A neural network can sustain and switch between different activity patterns to execute multiple behaviors. By monitoring the decision making for directional locomotion through motor circuit calcium imaging in?behaving Caenorhabditis elegans (C.?elegans), we reveal that C.?elegans determines the directionality of movements by establishing an imbalanced output between the forward and backward motor circuits and that it alters directions by switching between these imbalanced states. We further demonstrate that premotor interneurons modulate endogenous motoneuron activity to establish the output imbalance. Specifically, the UNC-7 and UNC-9 innexin-dependent premotor interneuron-motoneuron coupling prevents a balanced output state that leads to movements without directionality. Moreover, they act as shunts to decrease the backward-circuit activity, establishing a persistent bias for the high forward-circuit output state that results in the inherent preference of C.?elegans for forward locomotion. This study demonstrates that imbalanced motoneuron activity underlies directional movement and establishes gap junctions as critical modulators of the properties and outputs of neural circuits.     

Search and navigation in dynamic environments – from individual behaviors to population distributions

Animal movement receives widespread attention within ecology and behavior. However, much research is restricted within isolated sub-disciplines focusing on single phenomena such as navigation (e.g. homing behavior), search strategies (e.g. Levy flights) or theoretical considerations of optimal population dispersion (e.g. ideal free distribution). To help synthesize existing research, we outline a unifying conceptual framework that integrates individual-level behaviors and population-level spatial distributions with respect to spatio-temporal resource dynamics. We distinguish among (1) non-oriented movements based on diffusion and kinesis in response to proximate stimuli, (2) oriented movements utilizing perceptual cues of distant targets, and (3) memory mechanisms that assume prior knowledge of a target's location. Species' use of these mechanisms depends on life-history traits and resource dynamics, which together shape population-level patterns. Resources with little spatial variability should facilitate sedentary ranges, whereas resources with predictable seasonal variation in spatial distributions should generate migratory patterns. A third pattern, 'nomadism', should emerge when resource distributions are unpredictable in both space and time. We summarize recent advances in analyses of animal trajectories and outline three major components on which future studies should focus: (1) integration across alternative movement mechanisms involving links between state variables and specific mechanisms, (2) consideration of dynamics in resource landscapes or environments that include resource gradients in predictability, variability, scale, and abundance, and finally (3) quantitative methods to distinguish among population distributions. We suggest that combining techniques such as evolutionary programming and pattern oriented modeling will help to build strong links between underlying movement mechanisms and broad-scale population distributions.     

Responses of Neurons of the Extrastriate Area 21b of the Cat Brain Cortex to Changes in Orientation of Moving Visual Stimuli

We studied the responses of neurons of the extrastriate cortical area 21b of the cat to changes in orientation of the movements of visual stimuli within the receptive field (RF) of the neuron under study. Our experiments demonstrated that 24 of 108 cells (22%) responded differentially to a certain extent to orientation of the movements of visual stimuli. As a whole, neurons of the area 21b did not demonstrate fine tuning on the optimum angle of orientation. In many cases, neuronal responses to different orientations of the movement of visual stimulus depended significantly on specific parameters of this stimulus (its shape, dimensions, and contrast). Some directionally sensitive neurons responded to a change in orientation of the movement of visual stimuli by modification of the index of directionality. We also studied spatial organization of the RF of neurons with the presentation of stationary visual stimuli. Comparison of the neuronal responses to a change in orientation of the movements of stimuli and to presentation of stationary stimuli showed that the correlation between the orientation sensitivity of the neuron under study and the stationary functional organization of its RF was insignificant. We hypothesize that inhibitory processes and subthreshold influences from a space surrounding the RF play a special role in the formation of the neuronal responses generated in the associative visual cortical regions to visual stimulation.     

PAR proteins regulate microtubule dynamics at the cell cortex in C. elegans

BACKGROUND: The PAR proteins are known to be localized asymmetrically in polarized C. elegans, Drosophila, and human cells and to participate in several cellular processes, including asymmetric cell division and spindle orientation. Although astral microtubules are known to play roles in these processes, their behavior during these events remains poorly understood. RESULTS: We have developed a method that makes it possible to examine the residence time of individual astral microtubules at the cell cortex of developing embryos. Using this method, we found that microtubules are more dynamic at the posterior cortex of the C. elegans embryo compared to the anterior cortex during spindle displacement. We further observed that this asymmetry depends on the PAR-3 protein and heterotrimeric G protein signaling, and that the PAR-2 protein affects microtubule dynamics by restricting PAR-3 activity to the anterior of the embryo. CONCLUSIONS: These results indicate that PAR proteins function to regulate microtubule dynamics at the cortex during microtubule-dependent cellular processes.     

Neural dynamics of event segmentation in music: converging evidence for dissociable ventral and dorsal networks

The real world presents our sensory systems with a continuous stream of undifferentiated information. Segmentation of this stream at event boundaries is necessary for object identification and feature extraction. Here, we investigate the neural dynamics of event segmentation in entire musical symphonies under natural listening conditions. We isolated time-dependent sequences of brain responses in a 10 s window surrounding transitions between movements of symphonic works. A strikingly right-lateralized network of brain regions showed peak response during the movement transitions when, paradoxically, there was no physical stimulus. Model-dependent and model-free analysis techniques provided converging evidence for activity in two distinct functional networks at the movement transition: a ventral fronto-temporal network associated with detecting salient events, followed in time by a dorsal fronto-parietal network associated with maintaining attention and updating working memory. Our study provides direct experimental evidence for dissociable and causally linked ventral and dorsal networks during event segmentation of ecologically valid auditory stimuli.     

Orientational dynamics of T2 DNA during agarose gel electrophoresis: influence of gel concentration and electric field strength

The understanding, on a molecular level, of the mechanisms responsible for the improved separation in DNA gel electrophoresis when using modulated electric fields requires detailed information about conformational distribution and dynamics in the DNA/gel system. The orientational order due to electrophoretic migration ("electrophoretic orientation") is an interesting piece of information in this context that can be obtained through linear dichroism spectroscopy [M. Jonsson, B. Akerman, and B. Nordén, (1988) Biopolymers 27, 381-414]. The technique permits measurement of the orientation factor S of DNA (S = 1 corresponds to perfect orientation) within an electrophoretic zone in the gel during the electrophoresis. It is reported that the degree of orientation of T2 DNA [170 kilo base pairs (kpb)] is considerable (S = 0.17 in 1% agarose at 10 V/cm) compared to relatively modest orientations of short fragments found earlier (for 23-kbp DNA, S = 0.03 in 1% agarose at 10 V/cm), showing that large DNA coils are substantially deformed during the migration. Growth and relaxation dynamics of the orientational order of the T2 DNA are also reported, as functions of gel concentration (0.3-2%), electric field strength (0-40 V/cm), and pulse characteristics. The rise profile of the DNA orientation, when applying a constant field, is a nonmonotonic function that displays a pronounced overshoot, followed by a minor undershoot, before it reaches steady-state orientation (after 12 s in 1% agarose, 9 V/cm). The orientational relaxation in absence of field shows a multiexponential decay in a time region of some 10 s, when most of the DNA anisotropy has disappeared. A surprising phenomenon is a memory over minutes of the DNA/gel system to previous pulses: with two consecutive rectangular pulses (of the same polarity), the orientational overshoot and undershoot as a response to the second pulse are significantly reduced compared to the first pulse. The time required to recover 90% of their amplitudes is typically 1200 s (1% agarose, 9 V/cm), which may be compared to the time required to relax 90% of the DNA orientation, which is only 6 s. The major part of the over- and undershoot recovery is thus a reorganization of a system in which DNA is already randomly oriented. The different response amplitudes and relaxation times, including the amplitude and recovery time of the overshoot, of the orientational order of DNA in the electrophoretic gel have been studied as functions of gel concentration and field strength. The results are discussed against relevant theories of polymer dynamics.     

A maximum entropy analysis of protein orientations using fluorescence polarization data from multiple probes

Techniques have recently become available to label protein subunits with fluorescent probes at predetermined orientation relative to the protein coordinates. The known local orientation enables quantitative interpretation of fluorescence polarization experiments in terms of orientation and motions of the protein within a larger macromolecular assembly. Combining data obtained from probes placed at several distinct orientations relative to the protein structure reveals functionally relevant information about the axial and azimuthal orientation of the labeled protein segment relative to its surroundings. Here we present an analytical method to determine the protein orientational distribution from such data. The method produces the broadest distribution compatible with the data by maximizing its informational entropy. The key advantages of this approach are that no a priori assumptions are required about the shape of the distribution and that a unique, exact fit to the data is obtained. The relative orientations of the probes used for the experiments have great influence on information content of the maximum entropy distribution. Therefore, the choice of probe orientations is crucial. In particular, the probes must access independent aspects of the protein orientation, and two-fold rotational symmetries must be avoided. For a set of probes, a "figure of merit" is proposed, based on the independence among the probe orientations. With simulated fluorescence polarization data, we tested the capacity of maximum entropy analysis to recover specific protein orientational distributions and found that it is capable of recovering orientational distributions with one and two peaks. The similarity between the maximum entropy distribution and the test distribution improves gradually as the number of independent probe orientations increases. As a practical example, ME distributions were determined with experimental data from muscle fibers labeled with bifunctional rhodamine at known orientations with respect to the myosin regulatory light chain (RLC). These distributions show a complex relationship between the axial orientation of the RLC relative to the fiber axis and the azimuthal orientation of the RLC about its own axis. Maximum entropy analysis reveals limitations in available experimental data and supports the design of further probe angles to resolve details of the orientational distribution.     

Mitotic orientation in three dimensions determined from multiple projections.

The three-dimensional orientation of mitoses in mouse small intestinal crypts of Lieberkuhn was determined from multiple projections of the mitotic figures in whole mounts of isolated intestinal crypts. We found evidence of a significant orientational bias for mitoses whose daughter cells would be added along the long axis of the crypt, and thus conform to the maintenance of the cylindrical shape of the intestinal crypt. However, we also observed many mitoses whose progeny must be rearranged if the simple cylindrical shape of the intestinal crypt is to be maintained. Our results indicate that the ultimate behavior of progeny cells and hence of local tissue form may not strictly depend on the orientation of mitosis. The methods presented may also be used in the study of mitotic orientation in other tissues.     

Pristionchus pacificus vulva formation: polarized division, cell migration, cell fusion, and evolution of invagination

Tube formation is a widespread process during organogenesis. Specific cellular behaviors participate in the invagination of epithelial monolayers that form tubes. However, little is known about the evolutionary mechanisms of cell assembly into tubes during development. In Caenorhabditis elegans, the detailed step-to-step process of vulva formation has been studied in wild type and in several mutants. Here we show that cellular processes during vulva development, which involve toroidal cell formation and stacking of rings, are conserved between C. elegans and Pristionchus pacificus, two species of nematodes that diverged approximately 100 million years ago. These cellular behaviors are divided into phases of cell proliferation, short-range migration, and cell fusion that are temporally distinct in C. elegans but not in P. pacificus. Thus, we identify heterochronic changes in the cellular events of vulva development between these two species. We find that alterations in the division axes of two equivalent vulval cells from Left-Right cleavage in C. elegans to Anterior-Posterior division in P. pacificus can cause the formation of an additional eighth ring. Thus, orthogonal changes in cell division axes with alterations in the number and sequence of cell fusion events result in dramatic differences in vulval shape and in the number of rings in the species studied. Our characterization of vulva formation in P. pacificus compared to C. elegans provides an evolutionary-developmental foundation for molecular genetic analyses of organogenesis in different species within the phylum Nematoda.     

You name it--memory and delay govern first name dynamics

The adoption and abandonment of first names through time is a fascinating phenomenon that may shed light on social dynamics and the forces that determine cultural taste in general. Here we show that baby name dynamics is governed almost solely by deterministic forces, even though the emerging abundance statistics resembles the one obtained from a pure drift model. Exogenous events are shown to affect the name dynamics very rarely, and most of the year-to-year fluctuations around the deterministic trend may be attributed solely to demographic noise. We suggest that the rise and fall of a name reflect an "infection" process with delay and memory. The symmetry between adoption and abandonment speed emerges from our model without further assumptions.     

A parsimonious oscillatory model of handwriting

We propose an oscillatory model that is theoretically parsimonious, empirically efficient and biologically plausible. Building on Hollerbach’s (Biol Cybern 39:139–156, 1981) model, our Parsimonious Oscillatory Model of Handwriting (POMH) overcomes the latter’s main shortcomings by making it possible to extract its parameters from the trace itself and by reinstating symmetry between the \(x\) and \(y\) coordinates. The benefit is a capacity to autonomously generate a smooth continuous trace that reproduces the dynamics of the handwriting movements through an extremely sparse model, whose efficiency matches that of other, more computationally expensive optimizing methods. Moreover, the model applies to 2D trajectories, irrespective of their shape, size, orientation and length. It is also independent of the endeffectors mobilized and of the writing direction.     

MIGRATING CAMBIAL DOMAINS AND THE ORIGIN OF WAVY GRAIN IN XYLEM OF BROADLEAVED TREES

Anatomical analysis of wavy-grained xylem samples of Fraxinus, Acer, and Betula reveals a strong underlying pattern of orientational domains within the cambium. Domains are local areas in the cambium within which the orientation of pseudotransverse divisions of fusiform initial cells is predominately unidirectional rather than random. The orientation of ray splitting and ray uniting also tends to be unidirectional within domains. Because their boundaries migrate with time, domains are not fixed in shape or position. A specific group of initial cells may first be located in the interior of a domain, later near a boundary, and still later in another domain of opposite orientational prevalence. Domain patterns and their movements were delineated by classifying and mapping ray splitting and uniting events in temporal series of tangential sections of terminal late xylem. The domain patterns move slowly upward, preceding the similarly outlined, but noncoincident, grain pattern. A wavy grain pattern can be interpreted as being the result of a domain pattern of similar geometry. The efficacy of a domain pattern in eliciting a grain pattern is probably indirectly dependent upon the frequency of occurrence of pseudotransverse divisions and of ray splitting and uniting. The frequency is low in cambium producing straight-grained wood. Evidence of 10-fold and greater increases in frequency of ray splitting and uniting was found in straight-grained to wavy-grained transitional xylem.     

Is object search mediated by object-based or image-based representations?

Recent research suggests that visually specific memory representations for previously fixated objects are maintained during scene perception. Here we investigate the degree of visual specificity by asking whether the memory representations are image-based or object-based. To that end we measured the effects of object orientation on the time to search for a familiar object from amongst a set of 7 familiar distractors arranged in a circular array. Search times were found to depend on the relative orientations of the target object and the probe object for both familiar and novel objects. This effect was found to be partly an image matching effect but there was also an advantage shown for the object's canonical view for familiar objects. Orientation effects were maintained even when the target object was specified as having unique or similar shape properties relative to the distractors. Participants' eye movements were monitored during two of the experiments. Eye movement patterns revealed selection for object shape and object orientation during the search process. Our findings provide evidence for object representations during search that are detailed and share image-based characteristics with more high-level characteristics from object memory.     

The C. elegans touch response facilitates escape from predacious fungi

Predator-prey interactions are vital determinants in the natural selection of behavioral traits. Gentle touch to the anterior half of the body of Caenorhabditis elegans elicits an escape response in which the animal quickly reverses and suppresses exploratory head movements [1, 2]. Here, we investigate the ecological significance of the touch response in predator-prey interactions between C. elegans and predacious fungi that catch nematodes using constricting hyphal rings. We show that the constricting rings of Drechslerella doedycoides catch early larval stages with a diameter similar to the trap opening. There is a delay between the ring entry and ring closure, which allows the animal to withdraw from the trap before being caught. Mutants that fail to suppress head movements in response to touch are caught more efficiently than the wild-type. This demonstrates that the coordination of motor programs allows C. elegans to smoothly retract from a fungal noose and evade capture. Our results suggest that selective pressures imposed by predacious fungi have shaped the evolution of C. elegans escape behavior.