Evidence-Based Network Modelling to Simulate Nucleus Pulposus Multicellular Activity in Different Nutritional and Pro-Inflammatory Environments

Initiation of intervertebral disc degeneration is thought to be biologically driven. This reflects a process, where biochemical and mechanical stimuli affect cell activity (CA) that compromise the tissue strength over time. Experimental research enhanced our understanding about the effect of such stimuli on different CA, such as protein synthesis or mRNA expression. However, it is still unclear how cells respond to their native environment that consists of a “cocktail” of different stimuli that might locally vary. This work presents an interdisciplinary approach of experimental and in silico research to approximate Nucleus Pulposus CA within multifactorial biochemical environments. Thereby, the biochemical key stimuli glucose, pH, and the proinflammatory cytokines TNF-α and IL1β were considered that were experimentally shown to critically affect CA. To this end, a Nucleus Pulposus multicellular system was modelled. It integrated experimental findings from in vitro studies of human or bovine Nucleus Pulposus cells, to relate the individual effects of targeted stimuli to alterations in CA. Unknown stimulus-CA relationships were obtained through own experimental 3D cultures of bovine Nucleus Pulposus cells in alginate beads. Translation of experimental findings into suitable parameters for network modelling approaches was achieved thanks to a new numerical approach to estimate the individual sensitivity of a CA to each stimulus type. Hence, the effect of each stimulus type on a specific CA was assessed and integrated to approximate a multifactorial stimulus environment. Tackled CA were the mRNA expressions of Aggrecan, Collagen types I & II, MMP3, and ADAMTS4. CA was assessed for four different proinflammatory cell states; non-inflamed and inflamed for IL1β, TNF-α or both IL1β&TNF-α. Inflamed cell clusters were eventually predicted in a multicellular 3D agent-based model. Experimental results showed that glucose had no significant impact on proinflammatory cytokine or ADAMTS4 mRNA expression, whereas TNF-α caused a significant catabolic shift in most explored CA. In silico results showed that the presented methodology to estimate the sensitivity of a CA to a stimulus type importantly improved qualitative model predictions. However, more stimuli and/or further experimental knowledge need to be integrated, especially regarding predictions about the possible progression of inflammatory environments under adverse nutritional conditions. Tackling the multicellular level is a new and promising approach to estimate manifold responses of intervertebral disc cells. Such a top-down high-level network modelling approach allows to obtain information about relevant stimulus environments for a specific CA and could be shown to be suitable to tackle complex biological systems, including different proinflammatory cell states. The development of this methodology required a close interaction with experimental research. Thereby, specific experimental needs were derived from systematic in silico approaches and obtained results were directly used to enhance model predictions, which reflects a novelty in this research field. Eventually, the presented methodology provides modelling solutions suitable for multiscale approaches to contribute to a better understanding about dynamics over multiple spatial scales. Future work should focus on an amplification of the stimulus environment by integrating more key relevant stimuli, such as mechanical loading parameters, in order to better approximate native physiological environments.

Lateralized Readiness Potentials Recorded with Near-Threshold Auditory Stimuli in Subjects Simulating Hearing Loss

<b><i>Introduction:</i></b> Preparatory motor cortical responses like the lateralized readiness potential (LRP) may be useful in revealing persistent attempts to feign hearing loss. Previous studies suggest only a marginal effect of stimulus intensity on the amplitude of the LRP. However, this has not been investigated using low-intensity auditory stimuli to cue NoGo trials. We address this in an experiment where subjects were instructed not to give a manual response to low-instensity stimuli, a situation that is akin to simulating hearing loss. <b><i>Methods:</i></b> The LRP was recorded from normal hearing listeners (<i>N</i> = 10) with 500 and 4,000-Hz pure tones and trains of 4,000 Hz (2-1-2) tonebursts. Electrophysiologic data underwent processing to (i) analyze the effect of the stimulus type on the LRP, (ii) classify results according to manual response with both logistic regression and linear support vector machine (SVM) models, and (iii) derive auditory brainstem responses (ABRs) from the tonebursts. <b><i>Results:</i></b> The amplitude of the LRP did not differ between the 3 stimuli used to elicit the response. Single-trial electrode data from Go and NoGo trials were submitted to supervised binary classification, and the logistic regression model gave a mean accuracy of close to 0.7. The Jewett wave V latencies of the resultant ABRs from some subjects were found to increase between the high (Go) and low (NoGo) intensity tonebursts. <b><i>Conclusion:</i></b> This study shows that auditory stimulus type does not affect the amplitude of the LRP and that the response can be recorded with stimuli that are near the auditory threshold. It can also be recorded with transient stimuli, and this allows for the possibility of simultaneously recording other confirmatory measurements, like ABR.

Scintillating Starbursts: Concentric Star Polygons Induce Illusory Ray Patterns

Here, we introduce and explore Scintillating Starbursts, a stimulus type made up of concentric star polygons that induce illusory scintillating rays or beams. We test experimentally which factors, such as contrast and number of vertices, modulate how observers experience this stimulus class. We explain how the illusion arises from the interplay of known visual processes, specifically central versus peripheral vision, and interpret the phenomenology evoked by these patterns. We discuss how Starbursts differ from similar and related visual illusions such as illusory contours, grid illusions such as the pincushion grid illusion as well as moiré patterns.

Motor expertise and performance in sport-specific priming tasks: a systematic review and meta-analysis

Objective The present study aimed to summarize findings relevant to the influence of motor expertise on performance in sport-specific priming tasks and to examine potential moderators of this effect. Methodology Data were collected from the China National Knowledge Infrastructure (CNKI), PsychInfo, Medline, Google Scholar, Web of Science, Baidu Scholar and Sport Discus and Dissertation Abstracts Online databases from January 1999 to April 2020, supplemented by manual bibliographies and meeting minutes. Stata software was used to perform the meta-analysis. Study quality was evaluated systematically using the Newcastle-Ottawa scale (NOS). Standard mean differences (SMDs) with 95% CIs were calculated with a random-effects model. The Cochrane Q test and I2 statistic were used to evaluate heterogeneity. Begg funnel plots and Egger tests were conducted to assess publication bias. Results Nine articles (including 12 studies) were ultimately included in the meta-analysis. Significant heterogeneity was observed among these studies (Q = 44.42, P < 0.001, I2 = 75.2%) according to random-effects modeling. The results showed an overall advantage in favor of motor experts in sport-specific priming tasks (SMD = −1.01, 95% CI [−1.41 to −0.61]). However, the magnitude of that effect was moderated by sport type (interceptive sports/independent sports) and prime stimulus type (subliminal stimulus/supraliminal stimulus). No publication bias was detected by the Begg and Egger tests. Conclusions In general, compared with those of nonexperts, the responses of motor experts’ responses to a target stimulus are easier and faster when the prime and target stimuli are consistent. However, the magnitude of this effect is moderated by sport type and prime stimulus type.

Mismatch Between Risk and Response May Amplify Lethal and Non-lethal Effects of Humans on Wild Animal Populations

Human activity has rapidly transformed the planet, leading to declines of animal populations around the world through a range of direct and indirect pathways. Humans have strong numerical effects on wild animal populations, as highly efficient hunters and through unintentional impacts of human activity and development. Human disturbance also induces costly non-lethal effects by changing the behavior of risk-averse animals. Here, we suggest that the unique strength of these lethal and non-lethal effects is amplified by mismatches between the nature of risk associated with anthropogenic stimuli and the corresponding response by wild animals. We discuss the unique characteristics of cues associated with anthropogenic stimuli in the context of animal ecology and evolutionary history to explore why and when animals fail to appropriately (a) detect, (b) assess, and (c) respond to both benign and lethal stimuli. We then explore the costs of over-response to a benign stimulus (Type I error) and under-response to a lethal stimulus (Type II error), which can scale up to affect individual fitness and ultimately drive population dynamics and shape ecological interactions. Finally, we highlight avenues for future research and discuss conservation measures that can better align animal perception and response with risk to mitigate unintended consequences of human disturbance.