3D Hepatic Cultures Simultaneously Maintain Primary Hepatocyte and Liver Sinusoidal Endothelial Cell Phenotypes

Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes) and non-parenchymal (liver sinusoidal endothelial, LSEC) cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs) were cultured in a layered three-dimensional (3D) configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM), which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1) demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism, detoxification and signaling pathways in vitro

Extracellular matrix hydrogels from decellularized tissues: structure and function

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discusse

With peppermints you’re not my prince: Aroma modulates self-other integration

Recent studies showed that self-other integration, as indexed by the joint Simon effect (JSE), can be modulated by biasing participants towards particular (integrative vs. exclusive) cognitive-control states. Interestingly, there is evidence suggesting that such control states can be induced by particular odors: stimulating odors (e.g., peppermint aroma) seem to induce a more focused, exclusive state; relaxing odors (e.g., lavender aroma) are thought to induce a broader, more integrative state. In the present study, we tested the possible impact of peppermint and lavender aromas on self-other integration. Pairs of participants performed the joint Simon task in an either peppermint- or lavender-scented testing room. Results showed that both aromas modulated the size of the JSE, although they had a dissociable effect on reaction times (RTs) and percentage of errors (PEs). Whilst the JSE in RTs was found to be less pronounced in the peppermint group, compared to the lavender and no-aroma groups, the JSE in PEs was significantly more pronounced in the lavender group, compared to the peppermint and no-aroma group. These results are consistent with the emerging literature suggesting that the degree of self-other integration does not reflect a trait but a particular cognitive state, which can be biased towards excluding or integrating the other in one’s self-representation

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice

The plant leaf movement analyzer (PALMA): a simple tool for the analysis of periodic cotyledon and leaf movement in Arabidopsis thaliana

Wagner L, Schmal C, Staiger D, Danisman S. The plant leaf movement analyzer (PALMA): a simple tool for the analysis of periodic cotyledon and leaf movement in Arabidopsis thaliana. Plant Methods. 2017;13(1): 2.Background The analysis of circadian leaf movement rhythms is a simple yet effective method to study effects of treatments or gene mutations on the circadian clock of plants. Currently, leaf movements are analysed using time lapse photography and subsequent bioinformatics analyses of leaf movements. Programs that are used for this purpose either are able to perform one function (i.e. leaf tip detection or rhythm analysis) or their function is limited to specific computational environments. We developed a leaf movement analysis tool—PALMA—that works in command line and combines image extraction with rhythm analysis using Fast Fourier transformation and non-linear least squares fitting. Results We validated PALMA in both simulated time series and in experiments using the known short period mutant sensitivity to red light reduced 1 (srr1-1). We compared PALMA with two established leaf movement analysis tools and found it to perform equally well. Finally, we tested the effect of reduced iron conditions on the leaf movement rhythms of wild type plants. Here, we found that PALMA successfully detected period lengthening under reduced iron conditions. Conclusions PALMA correctly estimated the period of both simulated and real-life leaf movement experiments. As a platform-independent console-program that unites both functions needed for the analysis of circadian leaf movements it is a valid alternative to existing leaf movement analysis tools

Would Moral Enhancement Limit Freedom?

The proposal of moral enhancement as a valuable means to face the environmental, technological and social challenges that threaten the future of humanity has been criticized by a number of authors. One of the main criticisms has been that moral enhancement would diminish our freedom. It has been said that moral enhancement would lead enhanced people to lose their ‘freedom to fall’, that is, it would prevent them from being able to decide to carry out some morally bad actions, and the possibility to desire and carry out these bad actions is an essential ingredient of free will, which would thus be limited or destroyed—or so the argument goes. In this paper we offer an answer to this criticism. We contend that a morally enhanced agent could lose (to a large extent) the ‘freedom to fall’ without losing her freedom for two reasons. First, because we do not consider that a morally well-educated person, for whom the ‘freedom to fall’ is a remote option, is less free than an evildoer, and there is no reason to suppose that bioenhancement introduces a significant difference here. Second, because richness in the amount of alternative possibilities of action may be restored if the stated loss is compensated with an improvement in sensitivity and lucidity that can lead to seeing new options and nuances in the remaining possible actions

Putting ourselves in another’s skin: using the plasticity of self-perception to enhance empathy and decrease prejudice

The self is one the most important concepts in social cognition and plays a crucial role in determining questions such as which social groups we view ourselves as belonging to and how we relate to others. In the past decade, the self has also become an important topic within cognitive neuroscience with an explosion in the number of studies seeking to understand how different aspects of the self are represented within the brain. In this paper, we first outline the recent research on the neurocognitive basis of the self and highlight a key distinction between two forms of self-representation. The first is the “bodily” self, which is thought to be the basis of subjective experience and is grounded in the processing of sensorimotor signals. The second is the “conceptual” self, which develops through our interactions of other and is formed of a rich network of associative and semantic information. We then investigate how both the bodily and conceptual self are related to social cognition with an emphasis on how self-representations are involved in the processing and creation of prejudice. We then highlight new research demonstrating that the bodily and conceptual self are both malleable and that this malleability can be harnessed in order to achieve a reduction in social prejudice. In particular, we will outline strong evidence that modulating people’s perceptions of the bodily self can lead to changes in attitudes at the conceptual level. We will highlight a series of studies demonstrating that social attitudes towards various social out-groups (e.g. racial groups) can lead to a reduction in prejudice towards that group. Finally, we seek to place these findings in a broader social context by considering how innovations in virtual reality technology can allow experiences of taking on another’s identity are likely to become both more commonplace and more convincing in the future and the various opportunities and risks associated with using such technology to reduce prejudice

The joint Simon effect depends on perceived agency, but not intentionality, of the alternative action

A co-actor's intentionality has been suggested to be a key modulating factor for joint action effects like the joint Simon effect (JSE). However, in previous studies intentionality has often been confounded with agency defined as perceiving the initiator of an action as being the causal source of the action. The aim of the present study was to disentangle the role of agency and intentionality as modulating factors of the JSE. In Experiment 1, participants performed a joint go/nogo Simon task next to a co-actor who either intentionally controlled a response button with own finger movements (agency+/intentionality+) or who passively placed the hand on a response button that moved up and down on its own as triggered by computer signals (agency−/intentionality−). In Experiment 2, we included a condition in which participants believed that the co-actor intentionally controlled the response button with a Brain-Computer Interface (BCI) while placing the response finger clearly besides the response button, so that the causal relationship between agent and action effect was perceptually disrupted (agency−/intentionality+). As a control condition, the response button was computer controlled while the co-actor placed the response finger besides the response button (agency−/intentionality−). Experiment 1 showed that the JSE is present with an intentional co-actor and causality between co-actor and action effect, but absent with an unintentional co-actor and a lack of causality between co-actor and action effect. Experiment 2 showed that the JSE is absent with an intentional co-actor, but no causality between co-actor and action effect. Our findings indicate an important role of the co-actor's agency for the JSE. They also suggest that the attribution of agency has a strong perceptual basis