The emerging role of fatty acid binding protein 7 (FABP7) in cancers.

Fatty acid binding protein 7 (FABP7) is an intracellular protein involved in the uptake, transportation, metabolism, and storage of fatty acids (FAs). FABP7 is upregulated up to 20-fold in multiple cancers, usually correlated with poor prognosis. FABP7 silencing or pharmacological inhibition suggest FABP7 promotes cell growth, migration, invasion, colony and spheroid formation/increased size, lipid uptake, and lipid droplet formation. Xenograft studies show that suppression of FABP7 inhibits tumour formation and tumour growth, and improves host survival. The molecular mechanisms involve promotion of FA uptake, lipid droplets, signalling [focal adhesion kinase (FAK), proto-oncogene tyrosine-protein kinase Src (Src), mitogen-activated protein kinase kinase/p-extracellular signal-regulated kinase (MEK/ERK), and Wnt/ß-catenin], hypoxia-inducible factor 1-alpha (Hif1α), vascular endothelial growth factor A/prolyl 4-hydroxylase subunit alpha-1 (VEGFA/P4HA1), snail family zinc finger 1 (Snail1), and twist-related protein 1 (Twist1). The oncogenic capacity of FABP7 makes it a promising pharmacological target for future cancer treatments.

Human Crowds as Social Networks: Collective Dynamics of Consensus and Polarization.

A ubiquitous type of collective behavior and decision-making is the coordinated motion of bird flocks, fish schools, and human crowds. Collective decisions to move in the same direction, turn right or left, or split into subgroups arise in a self-organized fashion from local interactions between individuals without central plans or designated leaders. Strikingly similar phenomena of consensus (collective motion), clustering (subgroup formation), and bipolarization (splitting into extreme groups) are also observed in opinion formation. As we developed models of crowd dynamics and analyzed crowd networks, we found ourselves going down the same path as models of opinion dynamics in social networks. In this article, we draw out the parallels between human crowds and social networks. We show that models of crowd dynamics and opinion dynamics have a similar mathematical form and generate analogous phenomena in multiagent simulations. We suggest that they can be unified by a common collective dynamics, which may be extended to other psychological collectives. Models of collective dynamics thus offer a means to account for collective behavior and collective decisions without appealing to a priori mental structures.

Relative rate of expansion controls speed in one-dimensional pedestrian following.

Patterns of crowd behavior are believed to result from local interactions between pedestrians. Many studies have investigated the local rules of interaction, such as steering, avoiding, and alignment, but how pedestrians control their walking speed when following another remains unsettled. Most pedestrian models assume the physical speed and distance of others as input. The present study compares such "omniscient" models with "visual" models based on optical variables. We experimentally tested eight speed control models from the pedestrian- and car-following literature. Walking participants were asked to follow a leader (a moving pole) in a virtual environment, while the leader's speed was perturbed during the trial. In Experiment 1, the leader's initial distance was varied. Each model was fit to the data and compared. The results showed that visual models based on optical expansion (\(\dot{\theta }\)) had the smallest root mean square error in speed across conditions, whereas other models exhibited increased error at longer distances. In Experiment 2, the leader's size (pole diameter) was varied. A model based on the relative rate of expansion (\(\dot{\theta }/\theta \)) performed better than the expansion rate model (\(\dot{\theta }\)), because it is less sensitive to leader size. Together, the results imply that pedestrians directly control their walking speed in one-dimensional following using relative rate of expansion, rather than the distal speed and distance of the leader.

Is the neighborhood of interaction in human crowds metric, topological, or visual?

Global patterns of collective motion in bird flocks, fish schools, and human crowds are thought to emerge from local interactions within a neighborhood of interaction, the zone in which an individual is influenced by their neighbors. Both metric and topological neighborhoods have been reported in animal groups, but this question has not been addressed for human crowds. The answer has important implications for modeling crowd behavior and predicting crowd disasters such as jams, crushes, and stampedes. In a metric neighborhood, an individual is influenced by all neighbors within a fixed radius, whereas in a topological neighborhood, an individual is influenced by a fixed number of nearest neighbors, regardless of their physical distance. A recently proposed alternative is a visual neighborhood, in which an individual is influenced by the optical motions of all visible neighbors. We test these hypotheses experimentally by asking participants to walk in real and virtual crowds and manipulating the crowd's density. Our results rule out a topological neighborhood, are approximated by a metric neighborhood, but are best explained by a visual neighborhood that has elements of both. We conclude that the neighborhood of interaction in human crowds follows naturally from the laws of optics and suggest that previously observed "topological" and "metric" interactions might be a consequence of the visual neighborhood.

The emerging role of fatty acid binding protein 5 (FABP5) in cancers.

Fatty acid binding protein 5 (FABP5, or epidermal FABP) is an intracellular chaperone of fatty acid molecules that regulates lipid metabolism and cell growth. In patient-derived tumours, FABP5 expression is increased up to tenfold, often co-expressed with other cancer-related proteins. High tumoral FABP5 expression is associated with poor prognosis. FABP5 activates transcription factors (TFs) leading to increased expression of proteins involved in tumorigenesis. Genetic and pharmacological preclinical studies show that inhibiting FABP5 reduces protumoral markers, whereas elevation of FABP5 promotes tumour growth and spread. Thus, FABP5 might be a valid target for novel therapeutics. The evidence base is currently strongest for liver, prostate, breast, and brain cancers, and squamous cell carcinoma (SCC), which could represent relevant patient populations for any drug discovery programme.

Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance.

Cannabidiol, the main non-psychotropic constituent of cannabis, has potential as a treatment for anxiety-related disorders since it reduces learned fear expression and enhances fear extinction. The return of fear over time after successful extinction and stress-induced extinction resistance are potential barriers to the treatment of these disorders with extinction-based psychological therapy. In two experiments using rats subjected to auditory fear conditioning, we determined the effects of systemic cannabidiol treatment on (1) delayed extinction and later spontaneous fear recovery, and (2) extinction resistance caused by immediate extinction (the immediate extinction deficit (IED)). In Experiment 1, cannabidiol was given before delayed extinction occurring 24 h after conditioning, with extinction recall and spontaneous fear recovery tested drug-free 1 and 21 days after extinction, respectively. We found that cannabidiol had no effect on extinction recall but it prevented spontaneous fear recovery. In Experiment 2, the IED procedure was first validated, with immediate extinction occurring 30 min after conditioning. We confirmed that immediate extinction impaired extinction recall, compared to delayed extinction. Next, cannabidiol was given before immediate or no extinction, with extinction recall tested drug-free the next day. We found that cannabidiol rescued the IED, which did not involve effects on fear memory consolidation. In summary, cannabidiol prevented spontaneous fear recovery after delayed extinction and ameliorated extinction resistance caused by immediate extinction. Although the pharmacological mechanisms underlying these effects remain to be determined, our results add to evidence indicating that cannabidiol might prove useful as an adjunct for potentiating the psychological treatment of anxiety-related disorders.

URB597 induces subtle changes to aggression in adult Lister Hooded rats.

The endocannabinoid system has been implicated in both social and cognitive processing. The endocannabinoid metabolism inhibitor, URB597, dose-dependently improves non-social memory in adult Wistar and Sprague Dawley rats, whereas its effect on social interaction (SI) is affected by both rat strain and drug dose. Lister Hooded rats consistently respond differently to drug treatment in general compared with albino strains. This study sought to investigate the effects of different doses of URB597 on social and non-social memory in Lister Hooded rats, as well as analyzing the behavioral composition of the SI. Males were tested for novel object recognition (NOR), social preference (between an object and an unfamiliar rat), social novelty recognition (for a familiar vs. unfamiliar rat) and SI with an unfamiliar rat. URB597 (0.1 or 0.3 mg/kg) or vehicle was given 30 min before testing. During SI testing, total interaction time was assessed along with time spent on aggressive and explorative behaviors. Lister Hooded rats displayed expected non-social and social memory and social preference, which was not affected by URB597. During SI, URB597 did not affect total interaction time. However, the high dose increased aggression, compared to vehicle, and decreased anogenital sniffing, compared to the low dose of URB597. In summary, URB597 did not affect NOR, social preference or social recognition memory but did have subtle behavioral effects during SI in Lister hooded rats. Based on our findings we argue for the importance of considering strain as well as the detailed composition of behavior when investigating drug effects on social behavior.

Analysis of emergent patterns in crossing flows of pedestrians reveals an invariant of 'stripe' formation in human data.

When two streams of pedestrians cross at an angle, striped patterns spontaneously emerge as a result of local pedestrian interactions. This clear case of self-organized pattern formation remains to be elucidated. In counterflows, with a crossing angle of 180°, alternating lanes of traffic are commonly observed moving in opposite directions, whereas in crossing flows at an angle of 90°, diagonal stripes have been reported. Naka (1977) hypothesized that stripe orientation is perpendicular to the bisector of the crossing angle. However, studies of crossing flows at acute and obtuse angles remain underdeveloped. We tested the bisector hypothesis in experiments on small groups (18-19 participants each) crossing at seven angles (30° intervals), and analyzed the geometric properties of stripes. We present two novel computational methods for analyzing striped patterns in pedestrian data: (i) an edge-cutting algorithm, which detects the dynamic formation of stripes and allows us to measure local properties of individual stripes; and (ii) a pattern-matching technique, based on the Gabor function, which allows us to estimate global properties (orientation and wavelength) of the striped pattern at a time T. We find an invariant property: stripes in the two groups are parallel and perpendicular to the bisector at all crossing angles. In contrast, other properties depend on the crossing angle: stripe spacing (wavelength), stripe size (number of pedestrians per stripe), and crossing time all decrease as the crossing angle increases from 30° to 180°, whereas the number of stripes increases with crossing angle. We also observe that the width of individual stripes is dynamically squeezed as the two groups cross each other. The findings thus support the bisector hypothesis at a wide range of crossing angles, although the theoretical reasons for this invariant remain unclear. The present results provide empirical constraints on theoretical studies and computational models of crossing flows.

The visual coupling between neighbours explains local interactions underlying human 'flocking'.

Patterns of collective motion in bird flocks, fish schools and human crowds are believed to emerge from local interactions between individuals. Most 'flocking' models attribute these local interactions to hypothetical rules or metaphorical forces and assume an omniscient third-person view of the positions and velocities of all individuals in space. We develop a visual model of collective motion in human crowds based on the visual coupling that governs pedestrian interactions from a first-person embedded viewpoint. Specifically, humans control their walking speed and direction by cancelling the average angular velocity and optical expansion/contraction of their neighbours, weighted by visibility (1 - occlusion). We test the model by simulating data from experiments with virtual crowds and real human 'swarms'. The visual model outperforms our previous omniscient model and explains basic properties of interaction: 'repulsion' forces reduce to cancelling optical expansion, 'attraction' forces to cancelling optical contraction and 'alignment' to cancelling the combination of expansion/contraction and angular velocity. Moreover, the neighbourhood of interaction follows from Euclid's Law of perspective and the geometry of occlusion. We conclude that the local interactions underlying human flocking are a natural consequence of the laws of optics. Similar perceptual principles may apply to collective motion in other species.

Bumblebees display characteristics of active vision during robust obstacle avoidance flight.

Insects are remarkable flyers and capable of navigating through highly cluttered environments. We tracked the head and thorax of bumblebees freely flying in a tunnel containing vertically oriented obstacles to uncover the sensorimotor strategies used for obstacle detection and collision avoidance. Bumblebees presented all the characteristics of active vision during flight by stabilizing their head relative to the external environment and maintained close alignment between their gaze and flightpath. Head stabilization increased motion contrast of nearby features against the background to enable obstacle detection. As bees approached obstacles, they appeared to modulate avoidance responses based on the relative retinal expansion velocity (RREV) of obstacles and their maximum evasion acceleration was linearly related to RREVmax. Finally, bees prevented collisions through rapid roll manoeuvres implemented by their thorax. Overall, the combination of visuo-motor strategies of bumblebees highlights elegant solutions developed by insects for visually guided flight through cluttered environments.

Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats.

Endocannabinoid transmission is emerging as a target for treating anxiety-related disorders, given its regulation of fear extinction. Boosting anandamide levels via inhibition of its metabolism by fatty acid amide hydrolase (FAAH) can enhance extinction, whereas inhibiting monoacylglycerol lipase (MAGL) to elevate 2-arachidonoylglycerol levels can impair extinction. However, whether endocannabinoids regulate fear relapse over time or extinction resistance remains unclear. In two experiments using auditory fear conditioned rats, we examined the effects of the FAAH inhibitor URB597 and the MAGL inhibitor JZL184 administered systemically on 1) spontaneous fear recovery after delayed extinction, and 2) extinction resistance resulting from immediate extinction [the immediate extinction deficit (IED)]. In Experiment 1, URB597 or JZL184 was given immediately after delayed extinction occurring 24 h after conditioning. Extinction recall and spontaneous fear recovery were tested drug-free 1 and 21 days later, respectively. We found no effects of either drug on extinction recall or spontaneous fear recovery. In Experiment 2, URB597 or JZL184 was given before immediate extinction occurring 30 min after conditioning and extinction recall was tested drug-free the next day. We also examined the effects of propranolol, a beta-adrenoceptor antagonist that can rescue the IED, as a positive control. JZL184 enhanced fear expression and impaired extinction learning but we found no lasting effects of URB597 or JZL184 on cued extinction recall. Propranolol reduced fear expression but, unexpectedly, had no enduring effect on extinction recall. The results are discussed in relation to various methodological differences between previous studies examining endocannabinoid and adrenergic regulation of fear extinction.

In it together? The case for endocannabinoid-noradrenergic interactions in fear extinction.

Anxiety and trauma-related disorders, such as post-traumatic stress disorder (PTSD), are debilitating mental illnesses with great personal and socioeconomic costs. Examining memory formation and relevant behavioural responding associated with aversive stimuli may improve our understanding of the neurobiology underlying fear memory processing and PTSD treatment. The neurocircuitry underpinning learned fear and its inhibition through extinction is complex, involving synergistic interactions between different neurotransmitter systems in inter-connected brain areas. Endocannabinoid and noradrenergic transmission have both been implicated separately in fear memory processing and PTSD, but potential interactions between these systems in relation to fear extinction have received little attention to date. Their receptors are expressed together in brain areas crucial for fear extinction, which is enhanced by both cannabinoid and noradrenergic receptor activation in these areas. Moreover, cannabinoid signalling modulates the activity of locus coeruleus noradrenaline (NA) neurons and the release of NA in the medial prefrontal cortex, a brain area that is crucial for fear extinction. Interestingly, endocannabinoid-noradrenergic system interactions have been shown to regulate the encoding and retrieval of fear memory. Thus, noradrenergic regulation of fear extinction may also be driven indirectly in part via cannabinoid receptor signalling. In this perspective paper, we collate the available relevant literature and propose a synergistic role for the endocannabinoid and noradrenergic systems in regulating fear extinction, the study of which may further our understanding of the neurobiological substrates of PTSD and its treatment.

A day at the beach: Does visually perceived distance depend on the energetic cost of walking?

It takes less effort to walk from here to the Tiki Hut on the brick walkway than on the sandy beach. Does that influence how far away the Tiki Hut looks? The energetic cost of walking on dry sand is twice that of walking on firm ground (Lejeune et al., 1998). If perceived distance depends on the energetic cost or anticipated effort of walking (Proffitt, 2006), then the distance of a target viewed over sand should appear much greater than one viewed over brick. If perceived distance is specified by optical information (e.g., declination angle from the horizon; Ooi et al., 2001), then the distances should appear similar. Participants (N = 13) viewed a target at a distance of 5, 7, 9, or 11 m over sand or brick and then blind-walked an equivalent distance on the same or different terrain. First, we observed no main effect of walked terrain; walked distances on sand and brick were the same (p = 0.46), indicating that locomotion was calibrated to each substrate. Second, responses were actually greater after viewing over brick than over sand (p < 0.001), opposite to the prediction of the energetic hypothesis. This unexpected overshooting can be explained by the slight incline of the brick walkway, which partially raises the visually perceived eye level (VPEL) and increases the target distance specified by the declination angle. The result is thus consistent with the information hypothesis. We conclude that visually perceived egocentric distance depends on optical information and not on the anticipated energetic cost of walking.

Exit choice during evacuation is influenced by both the size and proportion of the egressing crowd.

It is unclear how building occupants take information from the social and built environment into account when choosing an egress route during emergency evacuation. Conflicting tendencies have been previously reported: to follow the crowd, to avoid congestion, and to avoid unknown egress routes alone. We hypothesize that these tendencies depend on an interaction between social influence and the affordances (opportunities for egress) of the built environment. In three virtual reality (VR) experiments (each N = 15), we investigated how social influence interacts with the affordances of available exits to determine exit choice. Participants were immersed in a crowd of virtual humans walking to the left or right exit, and were asked to walk to one of the exits. Experiment 1 tested the role of social influence by manipulating both the proportion of the crowd walking toward one exit (Crowd Proportion of 0 to 100%, in 10% increments) and the absolute number of virtual humans going to the exit (Crowd Size of 10 or 20). Experiment 2 tested the role of affordances by introducing two visible exit doors (1m width) in a closed room, and following the same protocol. Experiment 3 tested larger exit doors (3m width) that afford rapid egress for more people. In the small crowd, participants were increasingly likely to follow the majority as its proportion increased. In the large crowd, however, participants tended to avoid the more crowded exit if the doors were narrow (Experiment 2), but not if the doors were wide (Experiment 3). Participants tended to follow a 100% majority in all experiments, thereby avoiding going to an exit alone. We propose that the dynamics of exit choice can be understood in terms of competition between alternative egress routes: the attraction of an exit increases with the proportion of the crowd moving toward it, becoming dominant at 100%, but decreases with the absolute number in the crowd moving toward it, relative to the exit's affordance for egress.

Information Is Where You Find It: Perception as an Ecologically Well-Posed Problem.

Texts on visual perception typically begin with the following premise: Vision is an ill-posed problem, and perception is underdetermined by the available information. If this were really the case, however, it is hard to see how vision could ever get off the ground. James Gibson's signal contribution was his hypothesis that for every perceivable property of the environment, however subtle, there must be a higher order variable of information, however complex, that specifies it-if only we are clever enough to find them. Such variables are informative about behaviorally relevant properties within the physical and ecological constraints of a species' niche. Sensory ecology is replete with instructive examples, including weakly electric fish, the narwal's tusk, and insect flight control. In particular, I elaborate the case of passing through gaps. Optic flow is sufficient to control locomotion around obstacles and through openings. The affordances of the environment, such as gap passability, are specified by action-scaled information. Logically ill-posed problems may thus, on closer inspection, be ecologically well-posed.

Robust weighted averaging accounts for recruitment into collective motion in human crowds.

Agent-based models of 'flocking' and 'schooling' have shown that a weighted average of neighbor velocities, with weights that decay gradually with distance, yields emergent collective motion. Weighted averaging thus offers a potential mechanism of self-organization that recruits an increasing, but self-limiting, number of individuals into collective motion. Previously, we identified and modeled such a 'soft metric' neighborhood of interaction in human crowds that decays exponentially to zero at a distance of 4-5m. Here we investigate the limits of weighted averaging in humans and find that it is surprisingly robust: pedestrians align with the mean heading direction in their neighborhood, despite high levels of noise and diverging motions in the crowd, as predicted by the model. In three Virtual Reality experiments, participants were immersed in a crowd of virtual humans in a mobile head-mounted display and were instructed to walk with the crowd. By perturbing the heading (walking direction) of virtual neighbors and measuring the participant's trajectory, we probed the limits of weighted averaging. (1) In the 'Noisy Neighbors' experiment, the neighbor headings were randomized (range 0-90°) about the crowd's mean direction (±10° or ±20°, left or right); (2) in the 'Splitting Crowd' experiment, the crowd split into two groups (heading difference = 10-40°) and the proportion of the crowd in one group was varied (50-84%); (3) in the 'Coherent Subgroup' experiment, a perturbed subgroup varied in its coherence (heading SD = 0-2°) about a mean direction (±10° or ±20°) within a noisy crowd (heading range = 180°), and the proportion of the crowd in the subgroup was varied. In each scenario, the results were predicted by the weighted averaging model, and attraction strength (turning rate) increased with the participant's deviation from the mean heading direction, not with group coherence. However, the results indicate that humans ignore highly discrepant headings (45-90°). These findings reveal that weighted averaging in humans is highly robust and generates a common heading direction that acts as a positive feedback to recruit more individuals into collective motion, in a self-reinforcing cascade. Therefore, this 'soft' metric neighborhood serves as a mechanism of self-organization in human crowds.

Executing the homebound path is a major source of error in homing by path integration.

Path integration-the constant updating of position and orientation in an environment-is an important component of spatial navigation, however, its mechanisms are poorly understood. The aims of this study are (a) to test the encoding-error model of path integration, which focuses solely on encoding as a potential source of error, and (b) to develop a model of path integration that best predicts path integration errors. We tested the encoding-error model by independently measuring participants' encoding errors in distance and angle reproduction tasks, and then using those reproduction errors to predict individual participants' errors in a triangle completion task. We sampled the distribution of encoding errors using Monte Carlo methods to predict the homebound path, and then compared the predictions to observed triangle completion behavior. The correlation between predicted errors and actual errors in the triangle completion task was extremely weak, whereas an alternative model using execution error alone was sufficient to describe the observed errors. A model incorporating both encoding and execution errors best described the triangle completion errors. These results suggest that errors in executing the response may contribute more to overall errors in path integration than do encoding errors, challenging the assumption that errors reflect encoding alone. Errors in triangle completion might not arise from failing to know where you are, but from an inability to get back home. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Nonverbal leadership emergence in walking groups.

The mechanisms underlying the emergence of leadership in multi-agent systems are under investigation in many areas of research where group coordination is involved. Nonverbal leadership has been mostly investigated in the case of animal groups, and only a few works address the problem in human ensembles, e.g. pedestrian walking, group dance. In this paper we study the emergence of leadership in the specific scenario of a small walking group. Our aim is to propose a rigorous mathematical methodology capable of unveiling the mechanisms of leadership emergence in a human group when leader or follower roles are not designated a priori. Two groups of participants were asked to walk together and turn or change speed at self-selected times. Data were analysed using time-dependent cross correlation to infer leader-follower interactions between each pair of group members. The results indicate that leadership emergence is due both to contextual factors, such as an individual's position in the group, and to personal factors, such as an individual's characteristic locomotor behaviour. Our approach can easily be extended to larger groups and other scenarios such as team sports and emergency evacuations.

Bumblebees perceive the spatial layout of their environment in relation to their body size and form to minimize inflight collisions.

Animals that move through complex habitats must frequently contend with obstacles in their path. Humans and other highly cognitive vertebrates avoid collisions by perceiving the relationship between the layout of their surroundings and the properties of their own body profile and action capacity. It is unknown whether insects, which have much smaller brains, possess such abilities. We used bumblebees, which vary widely in body size and regularly forage in dense vegetation, to investigate whether flying insects consider their own size when interacting with their surroundings. Bumblebees trained to fly in a tunnel were sporadically presented with an obstructing wall containing a gap that varied in width. Bees successfully flew through narrow gaps, even those that were much smaller than their wingspans, by first performing lateral scanning (side-to-side flights) to visually assess the aperture. Bees then reoriented their in-flight posture (i.e., yaw or heading angle) while passing through, minimizing their projected frontal width and mitigating collisions; in extreme cases, bees flew entirely sideways through the gap. Both the time that bees spent scanning during their approach and the extent to which they reoriented themselves to pass through the gap were determined not by the absolute size of the gap, but by the size of the gap relative to each bee's own wingspan. Our findings suggest that, similar to humans and other vertebrates, flying bumblebees perceive the affordance of their surroundings relative their body size and form to navigate safely through complex environments.