A pathogen-derived metabolite induces microglial activation via odorant receptors

Microglia (MG), the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen-derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We hypothesized that odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, are involved in microglial activation by pathogen-derived small metabolites. We found that MG express high levels of two mouse ORs, Olfr110 and Olfr111, which recognize a pathogenic metabolite, 2-pentylfuran, secreted by Streptococcus pneumoniae. These interactions activate MG to engage in chemotaxis, cytokine production, phagocytosis, and reactive oxygen species generation. These effects were mediated through the G(alpha s)-cyclic adenosine monophosphate-protein kinase A-extracellular signal-regulated kinase and G(beta gamma)-phospholipase C-Ca2+ pathways. Taken together, our results reveal a novel interplay between the pathogen-derived metabolite and ORs, which has major implications for our understanding of microglial activation by pathogen recognition. Database Model data are available in the PMDB database under the accession number PM0082389.N

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

How 'who someone is' and 'what they did' influences gossiping about them.

To understand, predict, and help correct each other's actions we need to maintain accurate, up-to-date knowledge of people, and communication is a critical means by which we gather and disseminate this information. Yet the conditions under which we communication social information remain unclear. Testing hypotheses generated from our theoretical framework, we examined when and why social information is disseminated about an absent third party: i.e., gossiped. Gossip scenarios presented to participants (e.g., "Person-X cheated on their exam") were based on three key factors: (1) target (ingroup, outgroup, or celebrity), (2) valence (positive or negative), and (3) content. We then asked them (a) whether they would spread the information, and (b) to rate it according to subjective valence, ordinariness, interest level, and emotion. For ratings, the scenarios participants chose to gossip were considered to have higher valence (whether positive or negative), to be rarer, more interesting, and more emotionally evocative; thus showing that the paradigm was meaningful to subjects. Indeed, for target, valence, and content, a repeated-measures ANOVA found significant effects for each factor independently, as well as their interactions. The results supported our hypotheses: e.g., for target, more gossiping about celebrities and ingroup members (over strangers); for valence, more about negative events overall, and yet for ingroup members, more positive gossiping; for content, more about moral topics, with yet all domains of social content communicated depending on the situation-context matters, influencing needs. The findings suggest that social knowledge sharing (i.e., gossip) involves sophisticated calculations that require our highest sociocognitive abilities, and provide specific hypotheses for future examination of neural mechanisms

Money for us versus money for them: cross-cultural differences in sensitivity to rewards for ingroup and outgroup

Economic decisions often involve consideration of social groups, as when a decision has consequences not just for oneself but also for an in-group or out-group member. Culture—specifically, differences between Western individualistic and Eastern collectivist cultures—has direct influence on perception of social group identity. Yet, not many studies have investigated how culture might influence economic decision making involving social groups. The current study determined cultural influences on sensitivity to rewards directed towards their ingroup and outgroup. American and Korean students performed a simple card game, in which they earned money for ingroup and outgroup members by choosing from amongst four card decks each associated with different reward outcomes for the two groups. Performance on the card game showed a culture-by-reward-group interaction such that Koreans showed greater reward sensitivity for the ingroup than did Americans. These results demonstrate significant cross-cultural differences in the processing of rewards towards different social groups

Preference-based serial decisions are counterintuitively influenced by emotion regulation and conscientiousness.

Our decisions have a temporally distributed order, and different choice orders (e.g., choosing preferred items first or last) can lead to vastly different experiences. We previously found two dominant strategies (favorite-first and favorite-last) in a preference-based serial choice setting (the 'sushi problem'). However, it remains unclear why these two opposite behavioral patterns arise: i.e., the mechanisms underlying them. Here we developed a novel serial-choice task, using pictures based on attractiveness, to test for a possible shared mechanism with delay discounting, the 'peak-end' bias (i.e., preference for experienced sequences that end well), or working-memory capacity. We also collected psychological and clinical metric data on personality, depression, anxiety, and emotion regulation. We again found the two dominant selection strategies. However, the results of the delay, peak-end bias, and memory capacity tasks were not related to serial choice, while two key psychological metrics were: emotion regulation and conscientiousness (with agreeableness also marginally related). Favorite-first strategists actually regulated emotions better, suggesting better tolerance of negative outcomes. Whereas participants with more varied strategies across trials were more conscientious (and perhaps agreeable), suggesting that they were less willing to settle for a single, simpler strategy. Our findings clarify mechanisms underlying serial choice and show that it may reflect a unique ability to organize choices into sequences of events

Fabrication of SiCw/Ti(3)SiC(2)composites with improved thermal conductivity and mechanical properties using spark plasma sintering

High strength SiC whisker-reinforced Ti(3)SiC(2)composites (SiCw/Ti3SiC2) with an improved thermal conductivity and mechanical properties were fabricated by spark plasma sintering. The bending strength of 10 wt% SiCw/Ti(3)SiC(2)was 635 MPa, which was approximately 50% higher than that of the monolithic Ti3SiC2(428 MPa). The Vickers hardness and thermal conductivity (k) also increased by 36% and 25%, respectively, from the monolithic Ti(3)SiC(2)by the incorporation of 10 wt% SiCw. This remarkable improvement both in mechanical and thermal properties was attributed to the fine-grained uniform composite microstructure along with the effects of incorporated SiCw. The SiCw/Ti(3)SiC(2)can be a feasible candidate for the in-core structural application in nuclear reactors due to the excellent mechanical and thermal properties

Light-Designed Shark Skin-Mimetic Surfaces

Sharks, marine creatures that swim fast and have an antifouling ability, possess dermal denticle structures of micrometer-size. Because the riblet geometries on the denticles reduce the shear stress by inducing the slip of fluid parallel to the stream-wise direction, shark skin has the distinguished features of low drag and antifouling. Although much attention has been given to low-drag surfaces inspired from shark skin, it remains an important challenge to accurately mimic denticle structures in the micrometer scale and to finely control their structural features. This paper presents a novel method to create shark skin-mimetic denticle structures for low drag by exploiting a photoreconfigurable azopolymer. The light-designed denticle structure exhibits superior hydrophobicity and an antifouling effect as sharks do. This work suggests that our novel photoreconfiguration technology, mimicking shark skin and systematically manipulating various structural parameters, can be used in a reliable manner for diverse applications requiring low-drag surfaces. ©1

Chronic TGF beta stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin beta 3-Akt-GSK3 beta signaling

Chronic exposure to TGFβ, a frequent occurrence for tumor cells in the tumor microenvironment, confers more aggressive phenotypes on cancer cells by promoting their invasion and migration while at the same time increasing their resistance to the growth-inhibitory effect of TGFβ. In this study, a transdifferentiated (TD) A549 cell model, established by chronically exposing A549 cells to TGFβ, showed highly invasive phenotypes in conjunction with attenuation of Smad-dependent signaling. We show that Snail protein, the mRNA expression of which strongly correlates with a poor prognosis in lung cancer patients, was highly stable in TD cells after TGFβ stimulation. The increased protein stability of Snail in TD cells correlated with elevated inhibitory phosphorylation of GSK3β, resulting from the high Akt activity. Notably, integrin β3, whose expression was markedly increased upon sustained exposure to TGFβ, was responsible for the high Akt activity as well as the increased Snail protein stability in TD cells. Consistently, clinical database analysis on lung cancer patients revealed a negative correlation between overall survival and integrin β3 mRNA levels. Therefore, we suggest that the integrin β3-Akt-GSK3β signaling axis plays an important role in non-canonical TGFβ signaling, determining the invasive properties of tumor cells chronically exposed to TGFβ.

Rethinking United States Military Bases in East Asia

Created as part of the 2015 Jackson School for International Studies SIS 495: Task Force. Clark Sorensen, Task Force Advisor; Carmela Conroy, EvaluatorBackground: Abuses against local populations by US military members stationed in the Republic of Korea (ROK) and Okinawa, Japan have complicated regional diplomatic agendas and security relationships. The initial raison d'etre for a US presence in the region, the Cold War, no longer exists. According to the 2015 US National Security Strategy, a perpetual forward deployment in Northeast Asia is essential to US security interests. Increased capability and aggression of the People's Republic of China (PRC), the gradual rearmament of Japan, a resilient and nuclear Democratic People's Republic of Korea (DPRK) regime, and a changing security environment necessitates a reassessment of regional threats and the sustainability of the current regional US military presence