Eye Movements in Response to Pain-Related Feelings in the Presence of Low and High Cognitive Loads

The affective dimension of pain contributes to pain perception. Cognitive load may influence pain-related feelings. Eye tracking has proven useful for detecting cognitive load effects objectively by using relevant eye movement characteristics. In this study, we investigated whether eye movement characteristics differ in response to pain-related feelings in the presence of low and high cognitive loads. A set of validated, control, and pain-related sounds were applied to provoke pain-related feelings. Twelve healthy young participants (six females) performed a cognitive task at two load levels, once with the control and once with pain-related sounds in a randomized order. During the tasks, eye movements and task performance were recorded. Afterwards, the participants were asked to fill out questionnaires on their pain perception in response to the applied cognitive loads. Our findings indicate that an increased cognitive load was associated with a decreased saccade peak velocity, saccade frequency, and fixation frequency, as well as an increased fixation duration and pupil dilation range. Among the oculometrics, pain-related feelings were reflected only in the pupillary responses to a low cognitive load. The performance and perceived cognitive load decreased and increased, respectively, with the task load level and were not influenced by the pain-related sounds. Pain-related feelings were lower when performing the task compared with when no task was being performed in an independent group of participants. This might be due to the cognitive engagement during the task. This study demonstrated that cognitive processing could moderate the feelings associated with pain perception

Dual-specificity MAP kinase phosphatases in health and disease

Source at https://doi.org/10.1016/j.bbamcr.2018.09.002.It is well established that a family of dual-specificity MAP kinase phosphatases (MKPs) play key roles in the regulated dephosphorylation and inactivation of MAP kinase isoforms in mammalian cells and tissues. MKPs provide a mechanism of spatiotemporal feedback control of these key signalling pathways, but can also mediate crosstalk between distinct MAP kinase cascades and facilitate interactions between MAP kinase pathways and other key signalling modules. As our knowledge of the regulation, substrate specificity and catalytic mechanisms of MKPs has matured, more recent work using genetic models has revealed key physiological functions for MKPs and also uncovered potentially important roles in regulating the pathophysiological outcome of signalling with relevance to human diseases. These include cancer, diabetes, inflammatory and neurodegenerative disorders. It is hoped that this understanding will reveal novel therapeutic targets and biomarkers for disease, thus contributing to more effective diagnosis and treatment for these debilitating and often fatal conditions

A communicational perspective

Ludological Communication of Social Reality is about researching video games from a communicational perspective. Its purpose lies not only in researching, how video games can communicate about global reality, as it takes a much bigger role in the field of game studies and communications. The main argument of this thesis is that video games can communicate outside their intended purpose, and that they could be used effectively for such communication by studying structural elements and levels of the video game. With combination of theories from game studies, linguistics, philosophy, psychology and mathematics, a conceptual model of video game communication has been built, based on mass communication media. The results have shown that communicational elements can be found on all levels of story, player activities and design. Also that developed and intended purposes of the game are directly connected to the communication of the game, but not necessarily with each other

The Molecular Pathogenesis of EML4-ALK Driven Lung Cancer and Strategies to Overcome Clinical Resistance to ALK Inhibitors

A promising strategy to combat cancer drug resistance is to deploy rational upfront polytherapy that suppresses the survival and emergence of resistant tumor cells. The optimal initial combination strategy is unclear in most tumors with oncogenic receptor kinases because they typically engage multiple effector pathways, and which of these individual pathways (if any) is most critical to tumor cell survival is poorly defined. Here, I demonstrate in models of lung adenocarcinoma harboring the oncogenic ALK receptor kinase fusion (EML4-ALK) that the RAS-MAPK pathway, but not other known ALK effectors, is required for tumor cell survival. We reveal that EML4-ALK drives RAS-MAPK activation by engaging all three major RAS isoforms (H, N-, K-RAS), a signaling event that requires the HELP domain of EML4. MAPK pathway reactivation via either genomic amplification of KRASWT or downregulation of the MAPK phosphatase DUSP6 promoted resistance to ALK inhibition. Accordingly, upfront ALK and MEK co-inhibition enhanced both the magnitude and duration of initial response in EML4-ALK lung adenocarcinoma in vitro and in vivo models. Furthermore, genomic amplification (or gene duplication) of KRASWT or downregulation of DUSP6 was observed in ALK fusion positive lung adenocarcinoma patients with acquired ALK inhibitor resistance. Together, my findings provide insight into the function of RAS-MAPK signaling in EML4-ALK lung adenocarcinoma and rationale for upfront ALK-MEK co-inhibition to forestall resistance and improve patient outcomes