CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.

Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C16:0 ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice. Conditional deletion of CerS6 in hypothalamic neurons attenuates high-fat diet (HFD)-dependent weight gain and improves glucose metabolism. Specifically, CerS6 deficiency in neurons expressing pro-opiomelanocortin (POMC) or steroidogenic factor 1 (SF-1) alters feeding behavior and alleviates the adverse metabolic effects of HFD feeding on insulin sensitivity and glucose tolerance. POMC-expressing cell-selective deletion of CerS6 prevents the diet-induced alterations of mitochondrial morphology and improves cellular leptin sensitivity. Our experiments reveal functions of CerS6-derived ceramides in hypothalamic lipotoxicity, altered mitochondrial dynamics, and ER/mitochondrial stress in the deregulation of food intake and glucose metabolism in obesity.

The connection between stress, density, and speed in crowds.

Moving around in crowds is part of our daily lives, and we are used to the associated restriction of mobility. Nevertheless, little is known about how individuals experience these limitations. Such knowledge would, however, help to predict behavior, assess crowding, and improve measures for safety and comfort. To address this research gap, we conducted two studies on how constrained mobility affects physiological arousal as measured by mobile electrodermal activity (EDA) sensors. In study 1, we constrained walking speed by externally imposing a specific walking speed without physical proximity to another person, while, in study 2, we varied walking speed by increasing the number of people in a given area. In study 1, we confirmed previous findings showing that faster speeds led to statistically significantly higher levels of physiological arousal. The external limitations of walking speed, however, even if perceived as uncomfortable, did not increase physiological arousal. In the second study, subjects' speed was gradually reduced by density in a single-lane experiment. This study shows that physiological arousal increased statistically significant with increasing density and decreasing speed, suggesting that people experience more stress when their movement is restricted by proximity to others. The result of study 2 is even more significant given the results of study 1: When there are no other people around, arousal increases with walking speed due to the physiology of walking. This effect reverses when the speed must be reduced due to other people. Then the arousal increases at lower speeds.

Don't stop me now: Psychological effects of interrupting a moving pedestrian crowd and a video game.

Interruptions are a part of our everyday lives. They are inevitable in complex societies, especially when many people move from one place to another as a part of their daily routines. The main aim of this research is to understand the effects of interruptions on individuals from a psychological and crowd dynamics perspective. Two studies were conducted to investigate this issue, with each focusing on different types of interruptions and examining their psychological (emotion, motivation, arousal) and physiological (heart rate) components. Study 1 examined interruptions in a video game setting and systematically varied goal proximity (N = 61). It was hypothesized that being interrupted in the later stages of goal pursuit would create a high aroused impatience state, while interruptions in the earlier stages would produce a low aroused boredom state. However, the results showed that the hypothesized groupwise differences were not observed. Instead, interruptions created annoyance in all conditions, both psychologically and physiologically. Study 2 investigated interruptions in pedestrian crowds (N = 301) and used a basic motivational dichotomy of high and low motivation. In the experiments, crowds (80-100 participants) were asked to imagine that they were entering a concert hall consisting of a narrow bottleneck. The low motivation group reported feeling bored during the interruption, while the high motivation group reported feeling impatient. Additionally, a motivational decrease was observed for the high motivation group due to the interruption. This drop in motivation after the interruption is also reflected in the measured density (person/m2) in front of the bottleneck. Overall, both studies showed that interruption can have significant effects on individuals, including psychological and physiological impacts. The observed motivational decrease through interruption is particularly relevant for crowd management, but further investigation is needed to understand the context-specific effects of interruptions.

Waiting and walking with strangers: a socio-psychological pedestrian experiment on joint action in anonymous situations.

Research on pedestrian dynamics has generally dealt with temporary gatherings of people who do not know each other personally. These gatherings are often framed as highly individualized encounters in which social interactions play no or only a marginal role. However, recent research based on self-categorization theory showed the relevance of salient social identity for crowd dynamics. Drawing on the interactionist approach of social identity theory and the work of Erving Goffman and Alfred Schütz, this paper aims to show that anonymous encounters are carefully concerted social phenomena. The authors present the results of an exploratory social psychological experiment (N = 83), in which groups of participants were asked to wait for 5 min in a designated area with different communicative conditions and then to walk to a narrow exit. Based on the assumption that communication and conformity to expectations influences the behaviour of those present, we introduced four modifications during the waiting time and analysed questionnaire data and video recordings in a mixed-methods design. The results show that direct communication correlates with higher speed, cell phone use with greater distance to the nearest neighbour, and unexpected behaviour with slower movement.

Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity.

The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis.

Crowds in front of bottlenecks at entrances from the perspective of physics and social psychology.

This article presents an interdisciplinary study of physical and social psychological effects on crowd dynamics based on a series of bottleneck experiments. Bottlenecks are of particular interest for applications such as crowd management and design of emergency routes because they limit the performance of a facility. In addition to previous work on the dynamics within the bottleneck, this study focuses on the dynamics in front of the bottleneck, more specifically, at entrances. The experimental set-up simulates an entrance scenario to a concert consisting of an entrance gate (serving as bottleneck) and a corridor formed by barriers. The parameters examined are the corridor width, degree of motivation and priming of the social norm of queuing. The analysis is based on head trajectories and questionnaires. We show that the density of persons per square metre depends on motivation and also increases continuously with increasing corridor width, meaning that a density reduction can be achieved by a reduction of space. In comparison to other corridor widths observed, the narrowest corridor is rated as being fairer, more comfortable and as showing less unfair behaviour. Pushing behaviour is seen as ambivalent: it is rated as unfair and listed as a strategy for faster access.

Collective phenomena in crowds-Where pedestrian dynamics need social psychology.

This article is on collective phenomena in pedestrian dynamics during the assembling and dispersal of gatherings. To date pedestrian dynamics have been primarily studied in the natural and engineering sciences. Pedestrians are analyzed and modeled as driven particles revealing self-organizing phenomena and complex transport characteristics. However, pedestrians in crowds also behave as living beings according to stimulus-response mechanisms or act as human subjects on the basis of social norms, social identities or strategies. To show where pedestrian dynamics need social psychology in addition to the natural sciences we propose the application of three categories-phenomena, behavior and action. They permit a clear discrimination between situations in which minimal models from the natural sciences are appropriate and those in which sociological and psychological concepts are needed. To demonstrate the necessity of this framework, an experiment in which a large group of people (n = 270) enters a concert hall through two different spatial barrier structures is analyzed. These two structures correspond to everyday situations such as boarding trains and access to immigration desks. Methods from the natural and social sciences are applied. Firstly, physical measurements show the influence of the spatial structure on the dynamics of the entrance procedure. Density, waiting time and speed of progress show large variations. Secondly, a questionnaire study (n = 60) reveals how people perceive and evaluate these entrance situations. Markedly different expectations, social norms and strategies are associated with the two spatial structures. The results from the questionnaire study do not always conform to objective physical measures, indicating the limitations of models which are based on objective physical measures alone and which neglect subjective perspectives.

Histology in 3D: development of an online interactive student resource on epithelium.

Epithelium is an important and highly specialised tissue type that makes up the lining of inner and outer surfaces of the human body. It is proposed that a self-study tool adds to efficient learning and lecturing on this complicated topic in medical curricula. This paper describes the development and evaluation of an online interactive 3D resource on epithelium for undergraduate medical students. A first evaluation was carried out by means of an online survey (n = 37). The resource was evaluated positively on the website in general, its visual contents and its value and potential for the medical curriculum.