Cortactin mediated morphogenic cell movements during zebrafish (Danio rerio) gastrulation

Cell migration is essential to direct embryonic cells to specific sites at which their developmental fates are ultimately determined. However, the mechanism by which cell motility is regulated in embryonic development is largely unknown. Cortactin, a filamentous actin binding protein, is an activator of Arp2/3 complex in the nucleation of actin cytoskeleton at the cell leading edge and acts directly on the machinery of cell motility. To determine whether cortactin and Arp2/3 mediated actin assembly plays a role in the morphogenic cell movements during the early development of zebrafish, we initiated a study of cortactin expression in zebrafish embryos at gastrulating stages when massive cell migrations occur. Western blot analysis using a cortactin specific monoclonal antibody demonstrated that cortactin protein is abundantly present in embryos at the most early developmental stages. Immunostaining of whole-mounted embryo showed that cortactin immunoreactivity was associated with the embryonic shield, predominantly at the dorsal side of the embryos during gastrulation. In addition, cortactin was detected in the convergent cells of the epiblast and hypoblast, and later in the central nervous system. Immunofluorescent staining with cortactin and Arp3 antibodies also revealed that cortactin and Arp2/3 complex colocalized at the periphery and many patches associated with the cell-to-cell junction in motile embryonic cells. Therefore, our data suggest that cortactin and Arp2/3 mediated actin polymerization is implicated in the cell movement during gastrulation and perhaps the development of the central neural system as well.

Numerical Simulation of Waves Generated by Seafloor Movements

Waves generated by vertical seafloor movements are simulated by use of a fully nonlinear two-dimensional numerical wave tank. In the source region, the seafloor lifts to a designated height by a generation function. The numerical tests show that file linear theory is only valid for estimating the wave behaviors induced by the seafloor movements with a small amplitude, and the fully nonlinear numerical model should be adopted in the simulation of the wave generation by the large amplitude seafloor movements. Without the background surface waves, many numerical tests on the stable maximum elevations eta(max)(0) are carried out by both the linear theory and the fully nonlinear model. The results of two models are compared and analyzed. For the fully nonlinear model, the influences of the amplitudes and the horizontal lengths on eta(max)(0) are stronger than that of the characteristic duration times. Furthermore, results reveal that there are significant differences between the linear theory and the fully nonlinear model. When the influences of the background surface waves are considered, the corresponding numerical analyses reveal that with the fully nonlinear model the eta(max)(0) near-linearly varies with the wave amplitudes of the surface waves, and the eta(max)(0) has significant dependences on the wave lengths and the wave phases of the surface waves. In addition, the differences between the linear theory and the fully nonlinear model are still obvious, aid these differences are significantly affected by The wave parameters of the background surface waves, such as the wave amplitude, the wave length and the wave phase.

Dependency-Directed Localization of Software Bugs

Software bugs are violated specifications. Debugging is the process that culminates in repairing a program so that it satisfies its specification. An important part of debugging is localization, whereby the smallest region of the program that manifests the bug is found. The Debugging Assistant (DEBUSSI) localizes bugs by reasoning about logical dependencies. DEBUSSI manipulates the assumptions that underlie a bug manifestation, eventually localizing the bug to one particular assumption. At the same time, DEBUSSI acquires specification information, thereby extending its understanding of the buggy program. The techniques used for debugging fully implemented code are also appropriate for validating partial designs.

Dependency Directed Reasoning for Complex Program Understanding

Artificial Intelligence research involves the creation of extremely complex programs which must possess the capability to introspect, learn, and improve their expertise. Any truly intelligent program must be able to create procedures and to modify them as it gathers information from its experience. [Sussman, 1975] produced such a system for a 'mini-world'; but truly intelligent programs must be considerably more complex. A crucial stepping stone in AI research is the development of a system which can understand complex programs well enough to modify them. There is also a complexity barrier in the world of commercial software which is making the cost of software production and maintenance prohibitive. Here too a system which is capable of understanding complex programs is a necessary step. The Programmer's Apprentice Project [Rich and Shrobe, 76] is attempting to develop an interactive programming tool which will help expert programmers deal with the complexity involved in engineering a large software system. This report describes REASON, the deductive component of the programmer's apprentice. REASON is intended to help expert programmers in the process of evolutionary program design. REASON utilizes the engineering techniques of modelling, decomposition, and analysis by inspection to determine how modules interact to achieve the desired overall behavior of a program. REASON coordinates its various sources of knowledge by using a dependency-directed structure which records the justification for each deduction it makes. Once a program has been analyzed these justifications can be summarized into a teleological structure called a plan which helps the system understand the impact of a proposed program modification.

Gender and health: a social movement’s agenda for Big Pharma.

Social movements have an important new campaigning and organizing competence in new information communication technologies. These technologies also enable the members of social movements to readily research the accuracy of information: knowledge becomes globalized and readily accessible. In relation to Big Pharma, women’s social movements and social movements of the medicated intersect, and there is now a substantial challenge to Big Pharma both within developed and developing countries from the terrain of gender and health. This paper documents those challenges and looks towards their consequences in the future both in respect of Big Pharma but also in terms of 'academic' research

Animated virtual agents to cue user attention: comparison of static and dynamic deictic cues on gaze and touch responses

This paper describes an experiment developed to study the performance of virtual agent animated cues within digital interfaces. Increasingly, agents are used in virtual environments as part of the branding process and to guide user interaction. However, the level of agent detail required to establish and enhance efficient allocation of attention remains unclear. Although complex agent motion is now possible, it is costly to implement and so should only be routinely implemented if a clear benefit can be shown. Pevious methods of assessing the effect of gaze-cueing as a solution to scene complexity have relied principally on two-dimensional static scenes and manual peripheral inputs. Two experiments were run to address the question of agent cues on human-computer interfaces. Both experiments measured the efficiency of agent cues analyzing participant responses either by gaze or by touch respectively. In the first experiment, an eye-movement recorder was used to directly assess the immediate overt allocation of attention by capturing the participant’s eyefixations following presentation of a cueing stimulus. We found that a fully animated agent could speed up user interaction with the interface. When user attention was directed using a fully animated agent cue, users responded 35% faster when compared with stepped 2-image agent cues, and 42% faster when compared with a static 1-image cue. The second experiment recorded participant responses on a touch screen using same agent cues. Analysis of touch inputs confirmed the results of gaze-experiment, where fully animated agent made shortest time response with a slight decrease on the time difference comparisons. Responses to fully animated agent were 17% and 20% faster when compared with 2-image and 1-image cue severally. These results inform techniques aimed at engaging users’ attention in complex scenes such as computer games and digital transactions within public or social interaction contexts by demonstrating the benefits of dynamic gaze and head cueing directly on the users’ eye movements and touch responses.

ROSSI: Emergence of communication in Robots through Sensorimotor and Social Interaction

ROSSI: Emergence of communication in Robots through Sensorimotor and Social Interaction, T. Ziemke, A. Borghi, F. Anelli, C. Gianelli, F. Binkovski, G. Buccino, V. Gallese, M. Huelse, M. Lee, R. Nicoletti, D. Parisi, L. Riggio, A. Tessari, E. Sahin, International Conference on Cognitive Systems (CogSys 2008), University of Karlsruhe, Karlsruhe, Germany, 2008 Sponsorship: EU-FP7

'Psyching-up' and muscular force production

Tod, D. A., Iredale, F., Gill, N. (2003). 'Psyching-up' and muscular force production. Sports Medicine, 33 (1), 47-58. RAE2008

Modern religious movements in India.

http://www.archive.org/details/modernreligiousm025064mbp

Modeling the Possible Influences of Eye Movements on the Refinement of Cortical Direction Selectivity

The second-order statistics of neural activity was examined in a model of the cat LGN and V1 during free-viewing of natural images. In the model, the specific patterns of thalamocortical activity required for a Bebbian maturation of direction-selective cells in VI were found during the periods of visual fixation, when small eye movements occurred, but not when natural images were examined in the absence of fixational eye movements. In addition, simulations of stroboscopic reming that replicated the abnormal pattern of eye movements observed in kittens chronically exposed to stroboscopic illumination produced results consistent with the reported loss of direction selectivity and preservation of orientation selectivity. These results suggest the involvement of the oculomotor activity of visual fixation in the maturation of cortical direction selectivity.

Miniature Eye Movements Enhance Fine Spatial Details

Our eyes are constantly in motion. Even during visual fixation, small eye movements continually jitter the location of gaze. It is known that visual percepts tend to fade when retinal image motion is eliminated in the laboratory. However, it has long been debated whether, during natural viewing, fixational eye movements have functions in addition to preventing the visual scene from fading. In this study, we analysed the influence in humans of fixational eye movements on the discrimination of gratings masked by noise that has a power spectrum similar to that of natural images. Using a new method of retinal image stabilization18, we selectively eliminated the motion of the retinal image that normally occurs during the intersaccadic intervals of visual fixation. Here we show that fixational eye movements improve discrimination of high spatial frequency stimuli, but not of low spatial frequency stimuli. This improvement originates from the temporal modulations introduced by fixational eye movements in the visual input to the retina, which emphasize the high spatial frequency harmonics of the stimulus. In a natural visual world dominated by low spatial frequencies, fixational eye movements appear to constitute an effective sampling strategy by which the visual system enhances the processing of spatial detail.

Adaptive Neural Networks for Control of Movement Trajectories Invariant under Speed and Force Rescaling

This article describes two neural network modules that form part of an emerging theory of how adaptive control of goal-directed sensory-motor skills is achieved by humans and other animals. The Vector-Integration-To-Endpoint (VITE) model suggests how synchronous multi-joint trajectories are generated and performed at variable speeds. The Factorization-of-LEngth-and-TEnsion (FLETE) model suggests how outflow movement commands from a VITE model may be performed at variable force levels without a loss of positional accuracy. The invariance of positional control under speed and force rescaling sheds new light upon a familiar strategy of motor skill development: Skill learning begins with performance at low speed and low limb compliance and proceeds to higher speeds and compliances. The VITE model helps to explain many neural and behavioral data about trajectory formation, including data about neural coding within the posterior parietal cortex, motor cortex, and globus pallidus, and behavioral properties such as Woodworth's Law, Fitts Law, peak acceleration as a function of movement amplitude and duration, isotonic arm movement properties before and after arm-deafferentation, central error correction properties of isometric contractions, motor priming without overt action, velocity amplification during target switching, velocity profile invariance across different movement distances, changes in velocity profile asymmetry across different movement durations, staggered onset times for controlling linear trajectories with synchronous offset times, changes in the ratio of maximum to average velocity during discrete versus serial movements, and shared properties of arm and speech articulator movements. The FLETE model provides new insights into how spina-muscular circuits process variable forces without a loss of positional control. These results explicate the size principle of motor neuron recruitment, descending co-contractive compliance signals, Renshaw cells, Ia interneurons, fast automatic reactive control by ascending feedback from muscle spindles, slow adaptive predictive control via cerebellar learning using muscle spindle error signals to train adaptive movement gains, fractured somatotopy in the opponent organization of cerebellar learning, adaptive compensation for variable moment-arms, and force feedback from Golgi tendon organs. More generally, the models provide a computational rationale for the use of nonspecific control signals in volitional control, or "acts of will", and of efference copies and opponent processing in both reactive and adaptive motor control tasks.

Ligation of cell surface GRP78 with antibody directed against the COOH-terminal domain of GRP78 suppresses Ras/MAPK and PI 3-kinase/AKT signaling while promoting caspase activation in human prostate cancer cells.

We have previously shown that treatment of prostate cancer and melanoma cells expressing GRP78 on their cell surface with antibody directed against the COOH-terminal domain of GRP78 upregulates and activates p53 causing decreased cell proliferation and upregulated apoptosis. In this report, we demonstrate that treatment of 1-LN prostate cancer cells with this antibody decreases cell surface expression of GRP78, Akt(Thr308) and Akt(Ser473) kinase activities and reduces phosphorylation of FOXO, and GSK3beta. This treatment also suppresses activation of ERK1/2, p38 MAPK and MKK3/6; however, it upregulates MKK4 activity. JNK, as determined by its phosphorylation state, is subsequently activated, triggering apoptosis. Incubation of cells with antibody reduced levels of anti-apoptotic Bcl-2, while elevating pro-apoptotic BAD, BAX and BAK expression as well as cleaved caspases-3, -7, -8 and -9. Silencing GRP78 or p53 gene expression by RNAi prior to antibody treatment abrogated these effects. We conclude that antibody directed against the COOH-terminal domain of GRP78 may prove useful as a pan suppressor of proliferative/survival signaling in cancer cells expressing GRP78 on their cell surface.

Exploring the role of the substantia nigra pars reticulata in eye movements.

Experiments that demonstrated a role for the substantia nigra in eye movements have played an important role in our understanding of the function of the basal ganglia in behavior more broadly. In this review we explore more recent experiments that extend the role of the substantia nigra pars reticulata from a simple gate for eye movements to include a role in cognitive processes for eye movements. We review recent evidence suggesting that basal ganglia nuclei beyond the substantia nigra may also play a role in eye movements and the cognitive events leading up to the production of eye movements. We close by pointing out some unresolved questions in our understanding of the relationship of basal ganglia nuclei and eye movements.