Single Stimulus Research Articles

Did you even see that? visual sensory processing of single stimuli under different locomotor loads.

Modern living and working environments are more and more interspersed with the concurrent execution of locomotion and sensory processing, most often in the visual domain. Many job profiles involve the presentation of visual information while walking, for example in warehouse logistics work, where a worker has to manage walking to the correct aisle to pick up a package while being presented with visual information over data-glasses concerning the next order. Similar use-cases can be found in manufacturing jobs, for example in car montage assembly lines where next steps are presented via augmented reality headsets while walking at a slow pace. Considering the overall scarcity of cognitive resources available to be deployed to either the cognitive or motor processes, task performance decrements were found when increasing load in either domain. Interestingly, the walking motion also had beneficial effects on peripheral contrast detection and the inhibition of visual stream information. Taking these findings into account, we conducted a study that comprised the detection of single visual targets (Landolt Cs) within a broad range of the visual field (-40° to +40° visual angle) while either standing, walking, or walking with concurrent perturbations. We used questionnaire (NASA-TLX), behavioral (response times and accuracy), and neurophysiological data (ERPs and ERSPs) to quantify the effects of cognitive-motor interference. The study was conducted in a Gait Real-time Analysis Interactive Laboratory (GRAIL), using a 180° projection screen and a swayable and tiltable dual-belt treadmill. Questionnaire and behavioral measures showed common patterns. We found increasing subjective physical workload and behavioral decrements with increasing stimulus eccentricity and motor complexity. Electrophysiological results also indicated decrements in stimulus processing with higher stimulus eccentricity and movement complexity (P3, Theta), but highlighted a beneficial role when walking without perturbations and processing more peripheral stimuli regarding earlier sensory components (N1pc/N2pc, N2). These findings suggest that walking without impediments can enhance the visual processing of peripheral information and therefore help with perceiving non-foveal sensory content. Also, our results could help with re-evaluating previous findings in the context of cognitive-motor interference, as increased motor complexity might not always impede cognitive processing and performance.

Multiple fluorescence color transitions mediated by anion-π interactions and C-F covalent bond formation

The emission changes of fluorescent dyes under the influence of environmental changes or interaction with analytes are the basis for designing ratiometric fluorescent probes and logic gates. However, it is rare that only one external stimulus induces continuous fluorescent color changes in a fluorescent dye. In this paper, we report a cage-like molecule formed by two benzene rings and three imidazolium salts which produces continuous fluorescence wavelength changes when interacted with fluoride ions. Fluoride ions are first bound to the center of the cage under the action of anion-π interaction, and the (C−H)+···F– type ionic hydrogen bonds induce the blue-shift of fluorescence. The subsequent formation of C-F covalent bonds with fluoride ions makes the fluorophore wavelength continue to blue-shift, and finally obtains continuous multiple fluorescence changes caused by a single external stimulus. According to the fluorescence wavelength and intensity, six different fluorescence signal channels can be obtained, which can be encoded as six numbers from 0 to 5. We expect that this reaction process can find applications in quantitative anion recognition and molecular counters.

Escaping from multiple visual threats: modulation of escape responses in Pacific staghorn sculpin (Leptocottus armatus).

Fish perform rapid escape responses to avoid sudden predatory attacks. During escape responses, fish bend their bodies into a C-shape and quickly turn away from the predator and accelerate. The escape trajectory is determined by the initial turn (stage 1) and a contralateral bend (stage 2). Previous studies have used a single threat or model predator as a stimulus. In nature, however, multiple predators may attack from different directions simultaneously or in close succession. It is unknown whether fish are able to change the course of their escape response when startled by multiple stimuli at various time intervals. Pacific staghorn sculpin (Leptocottus armatus) were startled with a left and right visual stimulus in close succession. By varying the timing of the second stimulus, we were able to determine when and how a second stimulus could affect the escape response direction. Four treatments were used: a single visual stimulus (control); or two stimuli coming from opposite sides separated by a 0 ms (simultaneous treatment), 33 ms or 83 ms time interval. The 33 ms and 83 ms time intervals were chosen to occur either side of a predicted 60 ms visual escape latency (i.e. during stage 1). The 0 ms and 33 ms treatments influenced both the escape trajectory and the stage 1 turning angle, compared with a single stimulation, whereas the 83 ms treatment had no effect on the escape trajectory. We conclude that Pacific staghorn sculpin can modulate their escape trajectory only between stimulation and the onset of the response, but the escape trajectory cannot be modulated after the body motion has started.

Development of knitted reinforced structures with self-diagnostic function for composite applications

The research aims the development of knitted reinforcement structures for inducing self-diagnostic properties into knitted reinforced composites for structural health monitoring. Conductive carbon fiber was used in knitted inlaid structures as inlay yarns, and l × 1 Rib knitted base fabric of polyester filament yarn was used for knitting. The reinforcement’s conductive nature induced self-diagnostic properties into composites using correlation of mechanical damages and changes in electrical resistance values. Single and double stimuli layers and inlay patterns of 3 × 1, 6 × 1 and 9 × 1 was used to check their impact on self-diagnostic properties. Mechanical testing and real-time electrical resistance monitoring proved knitted structures as a solution to induce self-diagnostic properties into composite materials. Composites having double stimuli (conductive) layers exhibited better self-diagnostic properties than single stimuli layer composites, and the self-diagnostic properties also improved as the inlay pattern of reinforcement moved from 9 × 1 to 6 × 1 and 3 × 1 inlay. Such knitted reinforced self-diagnostic composites could be practically used in structural health monitoring applications, e.g., complicated structures of large buildings infrastructures and machinery which require record of each minor happening with structures to keep smooth and successful running of the system.

Recent Advances in Research on Molecular Mechanisms of Fungal Signaling

Biochemical signaling is one of the key mechanisms to coordinate a living organism in all aspects of its life. It is still enigmatic how exactly cells and organisms deal with environmental signals and irritations precisely because of the limited number of signaling proteins and a multitude of transitions inside and outside the cell. Many components of signaling pathways are functionally pleiotropic, which means they have several functions. A single stimulus often results in multiple responses, a distinct response can be triggered by numerous stimuli and signals initiated by different stimuli are often transduced via commonly used network components. This review sheds light on the most important molecular mechanisms of cellular signaling in fungi and consequently provides a comprehensive overview about the current state of research on the road to understand the impact of signal transduction in eukaryotic microorganisms.

Reward reduces the fission illusion in the sound-induced flash illusion.

Pairing a single visual stimulus with multiple auditory stimuli will lead to the illusory perception of multiple visual stimuli, which is known as sound-induced flash illusion (SIFI). The present study adopted the classic SIFI paradigm to investigate whether value-associated tasks could affect the SIFI. By adjusting the sequence of reward and nonreward conditions, we also examined the effect of reward history on SIFI. The results showed that the fission illusion was reduced when associated with momentary reward, demonstrating significantly higher accuracy and discriminability than the nonreward condition. However, the fusion illusion was not affected by the momentary reward, and the explanation was that the fusion illusion was not as stable as the fission illusion and disappeared across different trials and conditions. Moreover, the robustness of reward history in the present study was not as strong as previous studies have suggested, indicating that the effect of sound on the perceptual representation of visual stimuli is strong and robust to reward history. These findings demonstrated that the reward could reduce the SIFI and broaden the existing dichotomy of SIFI. New evidence for the operation of value-driven attention mechanisms is also provided, suggesting that the underlying value-driven attention operates across multiple sensory systems.

P 84 Altered sensorimotor integration of afferent inhibition in patients with complex regional pain syndrome

Introduction: The complex regional pain syndrome (CRPS) is a chronic pain condition which frequently results in sensorimotor dysfunction of the affected limb. With respect to pathophysiology an impaired interaction in sensorimotor cortex has been hypothesized 1 . Sensorimotor interactions can be assessed through transcranial magnetic stimulation (TMS) that is preceded by an electrical stimulation of peripheral motor or sensory nerves (short/ long afferent inhibition; SAI/LAI). Previous studies revealed only minor alterations of LAI using peripheral motor stimulation in CRPS 2 . This study uses a more comprehensive assessment of SAI and LAI, induced by motor and sensory peripheral stimulation, to assess interaction of the sensorimotor system in CRPS. Methods : 13 unilateral upper limb affected patients with CRPS (9 females, 54 ± 17.8 years) and 11 controls (HCs; 8 females, 52± 18.3 years) received TMS on either hemisphere. SAI and LAI were induced by a motor (m_) or sensory (s_) median nerve stimulation preceded by TMS with 20ms (m_SAI) and 200ms (m_LAI) or 23ms (s_SAI) and 203ms (s_LAI), respectively 3 . Twenty paired and single TMS stimuli were randomly applied for each condition. Results: Pain levels were 5.1±1.5/10 at rest and 7.4±2.1/10 during movements. ANOVA revealed a significant group effect for patients vs. HCs on the affected side (F=2.2, p=0.048). Post hoc tests were corrected for multiple comparisons and showed reduced inhibition in patients after sensory stimulation (s_SAI: t=-2.51, p=0.04; s_LAI: t=-2.53 p=0.038) and motor stimulation with ISI 200ms (m_LAI: t=-2.62, p=0.032). Afferent sensorimotor inhibition was lower in patients with longer disease duration (r=-0.66, p=0.014). Discussion: We demonstrate altered sensorimotor integration of afferent inhibition in CRPS. Since afferent inhibition after sensory stimulation is thought to be mediated via interconnections especially between Brodmann area 3b of somatosensory and the motor cortex, our results complement existing literature about maladaptive cortical plasticity of these regions in CRPS 4,5 . Impairment in LAI, that is thought to involve higher-order somatosensory cortical areas and the posterior parietal cortex is in line with existing literature on chronic pain 2,4 . Future longitudinal investigation should evaluate intra- and intercortical sensorimotor integration systematically in CRPS to better understand their impact in development of sensorimotor symptoms. Literature: 1 Harris AJ. Cortical origins of pathological pain. Lancet 1999. 2 Morgante et al. Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand. Mov Disord. 2017. 3 Sailer A, et al. Brain. 2003. 4 Chen et al. Modulation of motor cortex excitability by median nerve and digit stimulation. Exp Brain Res. 1999. 5 Pfannmöller et al. Investigations on maladaptive plasticity in the sensorimotor cortex of unilateral upper limb CRPS I patients. RNN. 2019.

Measuring task structure with transitional response times: Task representations are more than task sets.

The structure of task representations is widely studied with task-switching procedures in which the experimenter compares performance across predetermined categories of trial transitions (viz., switch costs). This approach has been productive, but relies on experimental assumptions about the relationships among stimulus-response mappings that define a set. Here, we develop a novel method of evaluating structure without relying on such assumptions. Participants responded to centrally presented stimuli and we computed the transitional response times (RTs; changes in RT as a function of specific response sequences) for each response combination. Conventional task-switch analyses revealed costs when the response switched from the left-side to the right or vice versa, but this switch cost was not affected by whether the stimuli belonged to a single category or to two distinct categories. In contrast, the transitional RT analysis provided fine-grained information about relationships among responses and how these relationships were affected by stimulus and response manipulations. Specifically, tasks containing a single stimulus category produced response chains in which neighboring responses had lower transitional RTs, while these chains were broken when two stimulus categories were used. We propose that the transitional RT approach offers a more detailed picture of the underlying task representation that reveals structure not detectable by conventional switch cost measures and does not require a priori assumptions about task organization.

Spinal Nociception is Facilitated during Cognitive Distraction

The nociceptive withdrawal reflex (NWR) is a behavioral response to protect the body from noxious stimuli. The spatial characteristics of the stimulus modulate the reflex response to prevent damage to the affected tissue. Interneurons in the deep dorsal horn in the spinal cord encode the relationship between stimulus characteristics and the magnitude of the NWR and are also likely integrating spatial information of the nociceptive stimulus. The aim of this study was to use the NWR to investigate whether the spinal spatial integration of a simultaneous stimulus is modulated by shifting the attention of the participant towards (attention) or away from (distraction) the stimulus. We hypothesized that the descending activity shapes the receptive fields of the spinal neurons encoding spatial integration of nociception. Twenty healthy volunteers participated in the study. Single and simultaneous stimuli were delivered through two stimulating electrodes located in the arch and on the lateral side in the sole of the foot. The NWR was quantified by electromyography from the Tibialis Anterior and Biceps Femoris muscles during baseline and active tasks (attention and distraction). During the baseline task, spatial summation of the NWR was evoked during simultaneous stimulation. During the distraction task, the NWR was significantly larger compared to baseline, regardless of the sites being stimulated (single and simultaneous stimuli). In contrast, the NWR recorded during the attention task did not differ from baseline. These results further support that the spinal NWR pathway is under descending control which can be modulated by cognitive processes. The NWRs recorded over both proximal and distal muscles were similarly affected by the tasks, suggesting that the descending control affects the lower leg spinal system, with no discrimination between spinal segments.

Response modalities and the cognitive architecture underlying action control: Intra-modal trumps cross-modal action coordination

Performing two actions at the same time usually hampers performance. Previous studies have demonstrated a strong impact of the particular effector systems on performance in multiple action control situations. However, an open question is whether performance is generally better or worse in situations in which two actions within the same effector system are coordinated (intra-modal actions: e.g., two pedal or two manual actions) compared to situations requiring two different effector systems (cross-modal actions: e.g., a manual combined with a vocal action). Performance differences can be predicated, among others, in the light of encapsulation accounts. Encapsulation of modules on the output side of processing would suggest that actions in two different modules can be triggered simultaneously without significant interference between the actions. Thus, cross-modal actions should lead to better performance compared to intra-modal actions. We investigated this issue in two basic experiments, in which participants responded to a single stimulus (thereby maximizing control over input and central processing stages) with one or two either intra-modal or cross-modal responses (manual-manual vs. manual-oculomotor/manual-vocal in Experiment 1/2, respectively). The results represent clear evidence for a performance advantage of intra-modal over cross-modal action control across both effector system combinations and independent of the particular spatial compatibility relation between responses. The results suggest performance benefits by taking advantage of integrated, holistic representations of intra-modal action compounds.

The importance of an exaggerated attention bottleneck for understanding psychopathy.

The psychopath has long captured the imagination. A name such as Ted Bundy evokes a morbid curiosity. The crimes committed by Bundy are so cruel that it is hard to imagine how someone could do such things. In this review we discuss evidence that exaggeration in an attention bottleneck is one mechanism that makes it possible for psychopathic individuals to be adept at focusing on a single stimulus feature or goal but struggle to process multiple streams of information simultaneously. This exaggeration may partly explain the behavioral, affective, and social deficits that are apparent among psychopathic individuals. Further research on this attentional mechanism may promote a science that adequately captures the complexity of psychopathic behavior and offers new avenues for intervention.

Two birds in the hand: Concurrent and switching cognitive flexibility in preschoolers

Cognitive flexibility, the ability to think of something in more than one way, has been studied in preschoolers from two different approaches. Within executive function research, most studies operationalize cognitive flexibility using sequential tasks in which children must think of a specific stimulus first in one way and then in another way (switching cognitive flexibility). In contrast, Piagetian multiplicative classification tasks also require cognitive flexibility by asking children to consider multiple dimensions of a single stimulus at the same time. Piagetian tasks are typically inductive and require abstraction skills. Although research with Piagetian tasks suggests that children are unable to consider multiple dimensions simultaneously until they reach the concrete operational stage, there is some evidence that preschoolers can coordinate two dimensions simultaneously in deductive tasks. In this study, we examined a deductive version of a matrix completion task in which preschoolers (N = 102) were asked to consider two dimensions of a given stimulus simultaneously. We show that 4- and 5-year-olds can succeed on this task and compare children’s performance on the matrix completion task with their performance on a widely used switching cognitive flexibility task, the Dimensional Change Card Sort. We discuss the implications of relating the two aspects of cognitive flexibility development.

Cocaine's effects on the reactivity of the medial prefrontal cortex to ventral tegmental area stimulation: optical imaging study in mice.

The prefrontal cortex (PFC) is modulated by dopaminergic and glutamatergic neurons that project from the ventral tegmental area (VTA) and disruption of this modulation might facilitate impulsive behaviors during cocaine intoxication. Here, we assessed the effects of acute cocaine (30 mg/kg, i.p.) on the reactivity of the PFC to VTA stimulation. Using a genetically encoded calcium indicator (GCaMP6f), we optically imaged the neuronal Ca2+ reactance in medial PFC (mPFC) in response to 'tonic-like' (5Hz) and 'phasic-like' (50 Hz) electrical VTA stimulation. The high temporal and spatial resolutions of our optical system allowed us to capture single Ca2+ neuronal transients from individual stimuli with 'tonic-like' stimulation and to visualize single neuronal activation evoked by 'phasic-like' VTA stimulation. 'Tonic-like' VTA stimulation induced a rapid increase in mean neuronal Ca2+ in mPFC followed by a plateau and recovery upon termination of stimulation. After cocaine, the mPFC sensitivity to 'tonic-like' VTA stimulation was attenuated, with a 50.4% reduction (P = 0.03) in the number of Ca2+ transients corresponding to single electrical stimuli but the recovery time was lengthened (4.30 ± 0.25 sec to 5.41 ± 0.24 sec, P = 0.03). 'Phasic-like' stimulation evoked a rapid Ca2+ fluorescence increase in mPFC with an immediate decay process, and while cocaine did not affect the peak response (7.17 ± 1.07% versus 7.13 ± 0.96%, P = 0.98) it shortened the recovery time to baseline (3.27 ± 0.11 sec versus 2.38 ± 0.23 sec, P = 0.005). Acute cocaine impairs reactivity of medial prefrontal cortex (mPFC) to ventral tegmental area stimulation, decreasing its sensitivity to 'tonic-like' stimulation and lengthening the recovery time to return to baseline while shortening it for phasic stimulation. These changes in mPFC might contribute to cocaine binging during intoxication.

Establishment of a novel mouse peritoneal dialysis-associated peritoneal injury model.

Peritoneal fibrosis induced by various factors during peritoneal dialysis (PD) can eventually lead to ultrafiltration failure and termination of PD treatment. The existing animal models are caused by a single stimulus, and cannot accurately simulate complex pathogenesis of peritoneal injury and fibrosis. We aim to develop an efficient and realistic mouse model of PD-associated peritoneal injury using daily intraperitoneal injection (I.P.) of human peritonitis PD effluent. Eight-week-old male C57BL/6 mice were classified into six groups: saline control; 2.5% PD fluid; 2.5% PD fluid + lipopolysaccharide (LPS); 4.25% PD fluid; 4.25% PD fluid + LPS; and peritonitis effluent. Mice received daily I.P. for 6weeks, and were sacrificed to determine peritoneal structural and functional damage, inflammation, and fibrosis. Mice in the peritonitis effluent group had low mortality. The submesothelial thickness in the peritonitis effluent group was significantly greater than that in the 2.5% PD fluid group. The peritonitis effluent group had increased expression of fibrosis markers (α-SMA, Collagen I, etc.), neutrophil granulocytes (MPO), and macrophages (CD68, F4/80) in the peritoneum based on immunohistochemical staining; and significantly higher expression of inflammation markers (IL-1β, IL-6, etc.) and fibrosis markers (TGF-β1, α-SMA, etc.) based on real-time qPCR. Modified peritoneal equilibration tests (PET) demonstrated that I.P. of peritonitis effluent reduced peritoneal ultrafiltration. Our novel animal model of PD-associated peritoneal injury faithfully simulates the clinical pathophysiological process. This animal model may be useful for study of the pathogenesis of PD-associated peritoneal injury and identification of novel treatments.

Bio-inspired fluorescence color-tunable soft actuators with a self-healing and reconfigurable nature

The adaptive behaviors of organisms in response to different environments can inspire the development of smart materials. These biomimetic color-changing actuating materials (BCCAMs) with complex shape memory (SM), self-healing, shape reconfigurable and reprocessing properties may be exactly what the flexible actuators/robots/electronic skins need. Here, we prepared an ultra-high strain (∼1600%) soft actuation material with fluorescence changes, self-healing, and SM performance under a single stimulus by a simple method. At the same time, we developed a simple strategy based on welding to achieve actuators that have a reconfiguring three-dimensional (3D) deformation and medium temperature reprocessing. The resulting 3D soft actuators can achieve effective coordination of these functions. Flexible actuators with multiple functions that can be triggered by a single switch are expected to have value in soft robots, flexible electronic skins, and so on.

DF-SSmVEP: Dual Frequency Aggregated Steady-State Motion Visual Evoked Potential Design with Bifold Canonical Correlation Analysis.

Recent advancements in Electroencephalographic (EEG) sensor technologies and signal processing algorithms have paved the way for further evolution of Brain Computer Interfaces (BCI) in several practical applications, ranging from rehabilitation systems to smart consumer technologies. When it comes to Signal Processing (SP) for BCI, there has been a surge of interest on Steady-State motion Visual Evoked Potentials (SSmVEP), where motion stimulation is used to address key issues associated with conventional light flashing/flickering. Such benefits, however, come with the price of being less accurate and having a lower Information Transfer Rate (ITR). From this perspective, this paper focuses on the design of a novel SSmVEP paradigm without using resources such as trial time, phase, and/or number of targets to enhance the ITR. The proposed design is based on the intuitively pleasing idea of integrating more than one motion within a single SSmVEP target stimuli, simultaneously. To elicit SSmVEP, we designed a novel and innovative dual frequency aggregated modulation paradigm, called the Dual Frequency Aggregated Steady-State motion Visual Evoked Potential (DF-SSmVEP), by concurrently integrating “Radial Zoom” and “Rotation” motions in a single target without increasing the trial length. Compared to conventional SSmVEPs, the proposed DF-SSmVEP framework consists of two motion modes integrated and shown simultaneously each modulated by a specific target frequency. The paper also develops a specific unsupervised classification model, referred to as the Bifold Canonical Correlation Analysis (BCCA), based on two motion frequencies per target. The corresponding covariance coefficients are used as extra features improving the classification accuracy. The proposed DF-SSmVEP is evaluated based on a real EEG dataset and the results corroborate its superiority. The proposed DF-SSmVEP outperforms its counterparts and achieved an average ITR of 30.7 ± 1.97 and an average accuracy of 92.5 ± 2.04, while the Radial Zoom and Rotation result in average ITRs of 18.35 ± 1 and 20.52 ± 2.5, and average accuracies of 68.12 ± 3.5 and 77.5 ± 3.5, respectively.

Fluorescence-color-changing biomimetic tough films with simultaneous shape-deformation triggered by pH

Stimuli-responsive materials with complex practical functions that could imitate certain behaviors of living organisms have wide potential applications in frontier fields. However, the fabrication of stimuli-responsive films with simultaneous change in fluorescence color and shape in response to a single stimulus, especially by a simple fabrication strategy, remains a challenge. Herein, a simple hydrogel-film-post crosslinking strategy is proposed to prepare films that exhibit fluorescence change accompanying with shape deformation under pH stimulus. The synchronous changes are realized by the combination of dynamic boron chemistry and pH-sensitive lanthanide complexes. Under different pH conditions, the protonation/deprotonation of the ligands coordinated to Eu3+ ions could generate switchable on/off fluorescence behavior, while the association/dissociation of borate ester bonds between 3-aminobenzeneboronic acid (SA-PBA) and polyvinyl alcohol (PVA) could lead to macroscopic deformation. The existence of borate ester bonds is beneficial to the mechanical properties of composite films. Under pH stimulus, the film-based artificial flower could simulate the flowering of natural flowers accompanying with color changes and the film-based gripper could grasp object with a visual signal, which demonstrates that the SA-PBA/PVA/EuL films have great potential for wide application.

Conceptual generalisation in fear conditioning using single and multiple category exemplars as conditional stimuli – electrodermal responses and valence evaluations generalise to the broader category

ABSTRACT Conceptual generalisation occurs when conditional responses generalise to novel stimuli from the same category. Past research demonstrates that physiological fear responses generalise across categories, however, conceptual generalisation of stimulus valence evaluations during fear conditioning has not been examined. We investigated whether conceptual generalisation, as indexed by electrodermal responses and stimulus evaluations, would occur, and differ after training with single or multiple conditional stimuli (CSs). Stimuli from two of four categories (vegetables, farm animals, clothing, and office supplies) were used as the CS+ (followed by an electric stimulus) or CS- (presented alone). Generalisation was assessed by presenting novel stimuli from the CS categories after acquisition, extinction, and reinstatement. One category exemplar was used as the CS+ and CS- in the single group, whereas three exemplars were used as the CS+ and CS- in the multiple group. Electrodermal responses generalised in acquisition and extinction but did not differ between groups. In the multiple group, CS evaluations generalised in acquisition and extinction, whereas generalisation was not evident in the single group. Training with multiple CSs also resulted in the extinction of stimulus valence. The current findings have implications for future research examining the generalisation of valence and for exposure-based treatments of anxiety.

Short-term bioelectric stimulation of collective cell migration in tissues reprograms long-term supracellular dynamics.

The ability to program collective cell migration can allow us to control critical multicellular processes in development, regenerative medicine, and invasive disease. However, while various technologies exist to make individual cells migrate, translating these tools to control myriad, collectively interacting cells within a single tissue poses many challenges. For instance, do cells within the same tissue interpret a global migration ‘command’ differently based on where they are in the tissue? Similarly, since no stimulus is permanent, what are the long-term effects of transient commands on collective cell dynamics? We investigate these questions by bioelectrically programming large epithelial tissues to globally migrate ‘rightward’ via electrotaxis. Tissues clearly developed distinct rear, middle, side, and front responses to a single global migration stimulus. Furthermore, at no point poststimulation did tissues return to their prestimulation behavior, instead equilibrating to a 3rd, new migratory state. These unique dynamics suggested that programmed migration resets tissue mechanical state, which was confirmed by transient chemical disruption of cell–cell junctions, analysis of strain wave propagation patterns, and quantification of cellular crowd dynamics. Overall, this work demonstrates how externally driving the collective migration of a tissue can reprogram baseline cell–cell interactions and collective dynamics, even well beyond the end of the global migratory cue, and emphasizes the importance of considering the supracellular context of tissues and other collectives when attempting to program crowd behaviors.

Preparation, Optimization, and Evaluation of Pellets Containing Mesalamine With Natural Gums For Colon Drug Delivery System

The purpose of the present work was to formulate colon-targeted mesalamine pellets containing gums of Moringa oleifera Lam. (MOG) and Cyamopsis tetragonolobus Taub. (CTG). Formulation of single stimuli mediated release is also difficult to target colon due to variation in the physiological condition, so in present work, pH dependent and enzyme degradation mechanisms are being used to release of drug at the colonic site. Extrusion and spheronization techniques were used for the preparation of pellets. For formulation optimization, factorial design study 32 was used for the selection of the optimized batch. It was found that high ratio of solvent 80:20 and 10% and 7.5% concentration of MOG and CTG respectively produce optimized pellets showed good physical properties and release for F8M and F8C and after coating it showed in vitro release at the colonic condition and in vivo roentgenographic images for targeting. As to say as advantages, spheronization and extrusion method was proved to have economized, whereas natural gums used to control release which added advantage as being as inert and biocompatible. This further formulation scope at industrial scales to reduce side effects of synthetic polymer and make it more biocompatible with the body.