Mantis Shrimp Locomotion: Coordination and Variation of Hybrid Metachronal Swimming.

Across countless marine invertebrates, coordination of closely spaced swimming appendages is key to producing diverse locomotory behaviors. Using a widespread mechanism termed hybrid metachronal propulsion, mantis shrimp swim by moving five paddle-like pleopods along their abdomen in a posterior to anterior sequence during the power stroke and a near-synchronous motion during the recovery stroke. Despite the ubiquity of this mechanism, it is not clear how hybrid metachronal swimmers coordinate and modify individual appendage movements to achieve a range of swimming capabilities. Using high-speed imaging, we measured pleopod kinematics of mantis shrimp (Neogonodactylus bredini), while they performed two swimming behaviors: burst swimming and taking off from the substrate. By tracking each of the five pleopods, we tested how stroke kinematics vary across swimming speeds and the two swimming behaviors. We found that mantis shrimp achieve faster swimming speeds through a combination of higher beat frequencies, smaller stroke durations, and partially via larger stroke angles. The five pleopods exhibit non-uniform kinematics that contribute to the coordination and forward propulsion of the whole system. Micro-hook structures (retinacula) connect each of the five pleopod pairs and differ in their attachment across pleopods-possibly contributing to passive kinematic control. We compare our findings in N. bredini to previous studies to identify commonalities across hybrid metachronal swimmers at high Reynolds numbers and centimeter scales. Through our large experimental dataset and by tracking each pleopod's movements, our study reveals key parameters by which mantis shrimp adjust and control their swimming, yielding diverse locomotor abilities.

Calculus migration characterization during Ho:YAG laser lithotripsy by high-speed camera using suspended pendulum method.

Calculus migration is a common problem during ureteroscopic laser lithotripsy procedure to treat urolithiasis. A conventional experimental method to characterize calculus migration utilized a hosting container (e.g., a "V" grove or a test tube). These methods, however, demonstrated large variation and poor detectability, possibly attributed to the friction between the calculus and the container on which the calculus was situated. In this study, calculus migration was investigated using a pendulum model suspended underwater to eliminate the aforementioned friction. A high-speed camera was used to study the movement of the calculus which covered zero order (displacement), first order (speed), and second order (acceleration). A commercialized, pulsed Ho:YAG laser at 2.1 µm, a 365-µm core diameter fiber, and a calculus phantom (Plaster of Paris, 10 × 10 × 10 mm3) was utilized to mimic laser lithotripsy procedure. The phantom was hung on a stainless steel bar and irradiated by the laser at 0.5, 1.0, and 1.5 J energy per pulse at 10 Hz for 1 s (i.e., 5, 10, and 15 W). Movement of the phantom was recorded by a high-speed camera with a frame rate of 10,000 FPS. The video data files are analyzed by MATLAB program by processing each image frame and obtaining position data of the calculus. With a sample size of 10, the maximum displacement was 1.25 ± 0.10, 3.01 ± 0.52, and 4.37 ± 0.58 mm for 0.5, 1, and 1.5 J energy per pulse, respectively. Using the same laser power, the conventional method showed <0.5 mm total displacement. When reducing the phantom size to 5 × 5 × 5 mm3 (one eighth in volume), the displacement was very inconsistent. The results suggested that using the pendulum model to eliminate the friction improved sensitivity and repeatability of the experiment. A detailed investigation on calculus movement and other causes of experimental variation will be conducted as a future study.

Water content contribution in calculus phantom ablation during Q-switched Tm:YAG laser lithotripsy.

Q-switched (QS) Tm:YAG laser ablation mechanisms on urinary calculi are still unclear to researchers. Here, dependence of water content in calculus phantom on calculus ablation performance was investigated. White gypsum cement was used as a calculus phantom model. The calculus phantoms were ablated by a total 3-J laser pulse exposure (20 mJ, 100 Hz, 1.5 s) and contact mode with N=15 sample size. Ablation volume was obtained on average 0.079, 0.122, and 0.391 mm3 in dry calculus in air, wet calculus in air, and wet calculus in-water groups, respectively. There were three proposed ablation mechanisms that could explain the effect of water content in calculus phantom on calculus ablation performance, including shock wave due to laser pulse injection and bubble collapse, spallation, and microexplosion. Increased absorption coefficient of wet calculus can cause stronger spallation process compared with that caused by dry calculus; as a result, higher calculus ablation was observed in both wet calculus in air and wet calculus in water. The test result also indicates that the shock waves generated by short laser pulse under the in-water condition have great impact on the ablation volume by Tm:YAG QS laser.

Residual alterations of brain electrical activity in clinically asymptomatic concussed individuals: an EEG study.

OBJECTIVE: To examine the neural substrates underlying performance on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and HeadRehab Virtual Reality (VR) balance and spatial modules in a concussed and control group. METHODS: Thirteen controls and seven concussed participants were fitted with a Geodesic 128-channel EEG cap and completed three assessments: EEG baseline, ImPACT testing, and VR balance and spatial modules. Concussed participants completed were tested within 8 (5 ± 1) days after injury. RESULTS: EEG power was significantly (p < .05) decreased in the concussed group over all testing modalities. EEG coherence was significantly (p < .05) increased in the concussed group during EEG baseline and ImPACT. For VR testing, two conditions showed significant (p < .05) increases in EEG coherence between ROIs, while two different conditions showed significant (p < .05) decreases in coherence levels. CONCLUSIONS: Concussed participants passed all clinical concussion testing tools, but showed pathophysiological dysfunction when evaluating EEG variables. SIGNIFICANCE: Concussed participants are able to compensate and achieve normal functioning due to recruiting additional brain networks. This allows concussed participants to pass clinical tests while still displaying electrophysiological deficits and clinicians must consider this information when making return-to-play decisions.

Modulation and experience of external stimuli: toward a science of experience and interoception.

The concept of interoception can be found in various writing over the past 100 or more years dating back to Sherrington, James and Lange. Professor György Adám that made American scientists increasingly aware of the importance of interoception with his 1967 book Interoception and Behavior. In this article we want to discuss two areas of research from out laboratory that have been influenced from this perspective. First, we will focus on electrocortical correlates of error detection during visuo-motor task and examine the manner in which an individual becomes aware of making an error as well as the way in which this awareness directs behavior on an ongoing basis. Second, we will examine hypnotic modulation of the pain experience and describe the manner in which electrocortical processes reflect the modulation and experience of pain. In this discussion, we suggest the importance of the anterior cingulate in not only modulating these processes in particular but also in its more general role as an interface between the limbic system and the neocortex and the integration of cognitive with emotional stimuli.

Motor-related cortical potentials accompanying enslaving effect in single versus combination of fingers force production tasks.

OBJECTIVES: This study examined behavioral indices and motor-related cortical potentials (MRCP) of the enslaving phenomenon (i.e. interdependency of finger movement) during isometric force production tasks using each of the four fingers separately and in combination. We examined MRCP preceding force production and those during the achievement of the desired force (ramp phase) and its maintenance (static phase). METHODS: Our experimental design systematically controlled the isometric force output, including both ramp and static phases of force production. We applied time-domain averaging of electroencephalographic single trials in order to extract 3 components of MRCP (Bereitshaftspotential, motor potentials, and motor monitoring potentials) preceding and accompanying force responses. RESULTS: We report two major findings. First, we found the index finger to be more independent, accurate, and to display the larger MRCP amplitude whereas the ring finger was more dependent, less accurate, and displayed smaller MRCP amplitude. Second, adding the neighboring finger when the ring finger produced the task significantly reduced its dependency on uninvolved fingers and increased the accuracy of both ramp and static phases which was not the case with the index finger. The amplitude of MRCP was increased when the ring finger produced the task in combination as compared to when the ring finger performed the task in isolation. In contrast, the amplitude of MRCP was significantly reduced when the index finger produced the task in combination with other fingers when compared to when the index finger performed the task in isolation. CONCLUSIONS: Overall, the amount of the fingers' dependency on the uninvolved fingers (e.g. amount of enslaving) during isometric force production tasks was inversely related with the amplitude of MRCP indicating the contribution of central mechanisms to the enslaving phenomenon.

Frontal lobe contributions to hypnotic susceptibility: a neuropsychological screening of executive functioning.

Current theory on the cognitive mechanisms of hypnotic experience suggests that hypnosis is mediated by a dissociation between contention-scheduling mechanisms and a supervisory attention system. This theory is based on neuropsychological research with frontal lobe dysfunction patients, who show performance deficits similar in executive functioning to hypnotized individuals. To test an extension of this theory, high hypnotically susceptible (n = 9) and low hypnotically susceptible (n = 7) participants were given four tests of executive functioning. In a baseline condition, high susceptible individuals performed significantly better on one of the four tests (the Wisconsin Card Sorting Test). The role of increased cognitive flexibility in hypnotic susceptibility is considered as a possible component of the dissociated control model of hypnosis.

Rate of force development and the lateralized readiness potential.

We examined the relationship between force and rate of force development aspects of movement dynamics and electroencephalogram motor components as reflected in the lateralized readiness potential (LRP). Using self-paced tasks, in Studies 1 and 3 we investigated whether differential speed and accuracy constraints in discrete and repetitive finger force production tasks influenced the LRP. These studies showed that speed tasks produced larger LRP than accuracy tasks regardless of whether the movement type was discrete or repetitive. In Studies 2 and 4 we studied four conditions with two levels of force and two levels of rate of force development. The largest LRPs were found with the greatest rate of force development. Overall, the four studies demonstrated that preparation for differential rates of force development is a major component reflected in the LRP.

Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta-protein generation.

An unusual intramembranous cleavage of the beta-amyloid precursor protein (APP) by gamma-secretase is the final step in the generation of amyloid beta-peptide (Abeta). Two conserved aspartates in transmembrane (TM) domains 6 and 7 of presenilin (PS) 1 are required for Abeta production by gamma-secretase. Here we report that the APP C-terminal fragments, C83 and C99, which are the direct substrates of gamma-secretase, can be coimmunoprecipitated with both PS1 and PS2. PS/C83 complexes were detected in cells expressing endogenous levels of PS. The complexes accumulate when gamma-secretase is inactivated either pharmacologically or by mutating the PS aspartates. PS1/C83 and PS1/C99 complexes were detected in Golgi-rich and trans-Golgi network-rich vesicle fractions. In contrast, complexes of PS1 with APP holoprotein, which is not the immediate substrate of gamma-secretase, occurred earlier in endoplasmic reticulum-rich vesicles. The major portion of intracellular Abeta at steady state was found in the same Golgi/trans-Golgi network-rich vesicles, and Abeta levels in these fractions were markedly reduced when either PS1 TM aspartate was mutated to alanine. Furthermore, de novo generation of Abeta in a cell-free microsomal reaction occurred specifically in these same vesicle fractions and was markedly inhibited by mutating either TM aspartate. Thus, PSs are complexed with the gamma-secretase substrates C83 and C99 in the subcellular locations where Abeta is generated, indicating that PSs are directly involved in the pathogenically critical intramembranous proteolysis of APP.

A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1.

Gamma-secretase-like proteolysis at site 3 (S3), within the transmembrane domain, releases the Notch intracellular domain (NICD) and activates CSL-mediated Notch signaling. S3 processing occurs only in response to ligand binding; however, the molecular basis of this regulation is unknown. Here we demonstrate that ligand binding facilitates cleavage at a novel site (S2), within the extracellular juxtamembrane region, which serves to release ectodomain repression of NICD production. Cleavage at S2 generates a transient intermediate peptide termed NEXT (Notch extracellular truncation). NEXT accumulates when NICD production is blocked by point mutations or gamma-secretase inhibitors or by loss of presenilin 1, and inhibition of NEXT eliminates NICD production. Our data demonstrate that S2 cleavage is a ligand-regulated step in the proteolytic cascade leading to Notch activation.

A complex of iron and nucleic acid catabolites is a signal that triggers differentiation in a freshwater protozoan.

The polymorphic ciliated protozoan Tetrahymena vorax can undergo differentiation from the microstomal form, which normally feeds on bacteria and other particulate matter, into the macrostomal cell type, which is capable of ingesting prey ciliates. The process is triggered by exposure of the microstome to an inducer contained in stomatin, an exudate of the prey. To establish the identity of the signal, stomatin was fractionated by combinations of cation exchange, HPLC, and TLC, and the fractions were assayed for biological activity. Although no single active fraction of purified inducer was obtained, all fractions with activity contained ferrous iron and the nucleic acid catabolites hypoxanthine (6-oxypurine) and uracil (2, 4-dioxopyrimidine), probably in a chelated form. The activity of synthetic complexes containing these three components is equivalent to stomatin. These results indicate a role for ferrous iron and its potential in chelated form to signal differentiation in certain protozoa and, perhaps, in other organisms as well.

Posttranslational modification and plasma membrane localization of the Drosophila melanogaster presenilin.

Mutations in two genes, presenilin 1 (PS1) and presenilin 2, are linked to early onset cases of familial Alzheimer's disease. The presenilins are thought to contribute to the pathogenesis of Alzheimer's disease by directly or indirectly affecting the proteolytic processing of the amyloid precursor protein. They have also been implicated in the proteolytic processing of Notch. In PS1-deficient mammalian cells, the proteolytic release of the Notch intracellular domain is reduced. Likewise, loss-of-function mutations in Drosophila presenilin (Psn) prevent the production of the intracellular Notch signaling fragment and lead to phenotypes resembling Notch mutants. Here we characterize the Drosophila Psn protein and demonstrate that it undergoes a proteolytic cleavage. We describe Psn expression at different developmental stages of the fly and show Psn localization near both apical and basal plasma membranes. Furthermore, we demonstrate that portions of the Psn protein span the plasma membrane in S2 cells.

Cardiovascular reactivity during hypnosis and hypnotic susceptibility: three studies of heart rate variability.

This paper was designed to examine the relationship between hypnotic susceptibility and cardiovascular measures, especially parasympathetic activity, in 3 separate studies. In these studies, neither heart rate nor heart rate variability differed between the high and low hypnotically susceptible individuals at the initial baseline. Furthermore, in the first study, experimental tasks designed to elicit differential sympathetic and parasympathetic cardiac responses demonstrated no interaction with hypnotic susceptibility. Overall, these 3 studies suggest that hypnotic susceptibility in itself is not associated with parasympathetic aspects of either basal cardiac states or cardiac responses. In addition, a hypnotic induction itself did not differentially influence parasympathetic activity for the high versus low susceptible individuals.

ES cell neural differentiation reveals a substantial number of novel ESTs.

We have used a method for synchronously differentiating murine embryonic stem (ES) cells into functional neurons and glia in culture. Using subtractive hybridization we isolated approximately 1200 cDNA clones from ES cell cultures at the neural precursor stage of neural differentiation. Pilot studies indicated that this library is a good source of novel neuro-embryonic cDNA clones. We therefore screened the entire library by single-pass sequencing. Characterization of 604 non-redundant cDNA clones by BLAST revealed 96 novel expressed sequence tags (ESTs) and an additional 197 matching uncharacterized ESTs or genomic clones derived from genome sequencing projects. With the exception of a handful of genes, whose functions are still unclear, most of the 311 known genes identified in this screen are expressed in embryonic development and/or the nervous system. At least 80 of these genes are implicated in disorders of differentiation, neural development and/or neural function. This study provides an initial snapshot of gene expression during early neural differentiation of ES cell cultures. Given the recent identification of human ES cells, further characterization of these novel and uncharacterized ESTs has the potential to identify genes that may be important in nervous system development, physiology and disease.

Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch.

Presenilin-1 (PS1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both Notch and beta-amyloid precursor protein (APP) within their trans- membrane domains. The activity that cleaves APP (called gamma-secretase) has properties of an aspartyl protease, and mutation of either of the two aspartate residues located in adjacent transmembrane domains of PS1 inhibits gamma-secretase processing of APP. We show here that these aspartates are required for Notch processing, since mutation of these residues prevents PS1 from inducing the gamma-secretase-like proteolysis of a Notch1 derivative. Thus PS1 might function in Notch cleavage as an aspartyl protease or di-aspartyl protease cofactor. However, the ER localization of PS1 is inconsistent with that hypothesis, since Notch cleavage occurs near the cell surface. Using pulse-chase and biotinylation assays, we provide evidence that PS1 binds Notch in the ER/Golgi and is then co-transported to the plasma membrane as a complex. PS1 aspartate mutants were indistinguishable from wild-type PS1 in their ability to bind Notch or traffic with it to the cell surface, and did not alter the secretion of Notch. Thus, PS1 appears to function specifically in Notch proteolysis near the plasma membrane as an aspartyl protease or cofactor.

Human gamma band activity and perception of a gestalt.

Neuronal oscillations in the gamma band (above 30 Hz) have been proposed to be a possible mechanism for the visual representation of objects. The present study examined the topography of gamma band spectral power and event-related potentials in human EEG associated with perceptual switching effected by rotating ambiguous (bistable) figures. Eleven healthy human subjects were presented two rotating bistable figures: first, a face figure that allowed perception of a sad or happy face depending on orientation and therefore caused a perceptual switch at defined points in time when rotated, and, second, a modified version of the Rubin vase, allowing perception as a vase or two faces whereby the switch was orientation-independent. Nonrotating figures served as further control stimuli. EEG was recorded using a high-density array with 128 electrodes. We found a negative event-related potential associated with the switching of the sad-happy figure, which was most pronounced at central prefrontal sites. Gamma band activity (GBA) was enhanced at occipital electrode sites in the rotating bistable figures compared with the standing stimuli, being maximal at vertical stimulus orientations that allowed an easy recognition of the sad and happy face or the vase-faces, respectively. At anterior electrodes, GBA showed a complementary pattern, being maximal when stimuli were oriented horizontally. The findings support the notion that formation of a visual percept may involve oscillations in a distributed neuronal assembly.

A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain.

Signalling through the receptor protein Notch, which is involved in crucial cell-fate decisions during development, requires ligand-induced cleavage of Notch. This cleavage occurs within the predicted transmembrane domain, releasing the Notch intracellular domain (NICD), and is reminiscent of gamma-secretase-mediated cleavage of beta-amyloid precursor protein (APP), a critical event in the pathogenesis of Alzheimer's disease. A deficiency in presenilin-1 (PS1) inhibits processing of APP by gamma-secretase in mammalian cells, and genetic interactions between Notch and PS1 homologues in Caenorhabditis elegans indicate that the presenilins may modulate the Notch signalling pathway. Here we report that, in mammalian cells, PS1 deficiency also reduces the proteolytic release of NICD from a truncated Notch construct, thus identifying the specific biochemical step of the Notch signalling pathway that is affected by PS1. Moreover, several gamma-secretase inhibitors block this same step in Notch processing, indicating that related protease activities are responsible for cleavage within the predicted transmembrane domains of Notch and APP. Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling.

Evidence for a physical interaction between presenilin and Notch.

Genetic analyses in Caenorhabditis elegans demonstrate that sel-12 and hop-1, homologues of the Alzheimer's disease-associated presenilin genes, modify signaling through LIN-12 and GLP-1, homologues of the Notch cell surface receptor. To gain insight into the biochemical basis of this genetic interaction, we tested the possibility that presenilin-1 (PS1) physically associates with the Notch1 receptor in mammalian cells. Notch1 and PS1 coimmunoprecipitated from transiently transfected human embryonic kidney 293 cell lysates in a detergent-sensitive manner, consistent with a noncovalent physical association between the two proteins. The interaction predominantly occurred early in the secretory pathway prior to Notch cleavage in the Golgi, because PS1 immunoprecipitation preferentially recovered the full-length Notch1 precursor. When PS1 was immunoprecipitated from 293 cells that had been metabolically labeled with [35S]methionine and [35S]cysteine, Notch1 was the primary protein detected in PS1 immunoprecipitates, suggesting that this interaction is specific. Furthermore, endogenous Notch and presenilin coimmunoprecipitated from cultured Drosophila cells, indicating that physical interaction can occur at physiological expression levels. These results suggest that the genetic relationship between presenilins and the Notch signaling pathway derives from a direct physical association between these proteins in the secretory pathway.

Movement-related potentials with reference to isometric force output in discrete and repetitive tasks.

This study investigates whether different speed and accuracy constraints in discrete and repetitive index finger isometric force-production tasks influence the characteristics of the movement-related potentials (MRP) preceding and accompanying these tasks. Three components of MRP (Bereitschaftspotential, BP, motor potential, MP, and movement-monitoring potential, MMP) associated with isometric force output were identified and examined. Our principal finding for the MRP amplitude showed that only MMP, not BP and MP, was enhanced at higher rates of force development for both speed and accuracy tasks. That is to say, there was a high correlation between MMP peak amplitude and the rate of force development for both repetitive and discrete force-production tasks. Additionally, the amplitude of MMP was consistently higher for fast, rather than accurate, force outputs. Moreover, the results from analysis of MRP onset times suggest that, in general, the MRP begin earlier for the fast force output than for the accurate force output.

Dynamical aspects of motor and perceptual processes in schizophrenic patients and healthy controls.

The present study examined the temporal stationarity of the performance of 16 schizophrenic patients and 16 controls matched for age and sex in a bimanual coordination task and a perceptual task. In the motor task, rhythmic finger oscillations (alternating activity of homologue muscle groups) at increasing speed levels resulted in two measures, the preferred oscillation frequency and the critical frequency at which phase transitions (change towards simultaneous activity of homologue muscle groups) occurred. A measure of local dimensional complexity (pointwise D2 or PD2), which is a measure of non-linear dynamics, was determined for the acceleration profiles of the subjects' movements. Schizophrenics exhibited less stable movement dynamics than controls in horizontal finger cycling, indicated by a lower ratio critical/preferred frequency (critical ratio) and by higher means and standard deviations of the pointwise D2. In vertical cycling, the critical ratio did not differentiate between groups, while PD2 means and standard deviations did. Groups also differed specifically in perception of two ambiguous figures (Schroeder stairs and Rubin vase). Schizophrenics showed significantly higher reversal rates for the Rubin vase and a differential perceptive in comparison to controls in the perception of the Schroeder stairs. Measures of perceptual and motor stability were unrelated, which suggests that perceptual and motor processes are not influenced by a common underlying mechanism.