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

Illegal corporate behavior and the value of firms

[[abstract]]This paper explores the relationships between illegal corporate behaviors, the value of firms, and economic conditions.Assuming the manager and the board both maximize shareholders’ value. The result shows that the most severe situations occur in big firms when businesses prosper. As long as punishment would not cause a firm to collapse, a success in illegality would discourage future crimes, while failures breed further wrongdoings. In addition, the temptation for future illegality is much less for the successful than the failed, meaning that the losers struggle harder to recover what has been lost than the winners trying to garner more

Environmental tobacco smoke and arsenic methylation capacity are associated with urothelial carcinoma

Cigarette smoking, exposure to secondhand smoke, and arsenic exposure are well known risk factors for developing urothelial carcinoma (UC). We investigated the combined effects of cigarette smoking, exposure to secondhand smoke, and the presence of urinary total arsenic on the risk of developing UC. Methods: We conducted a hospital-based, case–control study involving 261 UC patients and 672 cancer-free control individuals between September 2002 and May 2009. Results: Individuals who had smoked 100 cigarettes in their lifetime (ever smokers) and had a high urinary total arsenic level, had increased risks of developing UC (3.20-fold and 6.45-fold greater), respectively, compared to individuals who were never smokers and had a low urinary total arsenic level. Individuals who had high urinary total arsenic levels and had been exposed to secondhand smoke, and individuals with high urinary arsenic levels who had not been exposed to secondhand smoke, had increased chances (2.71-fold and 5.00-fold greater, respectively) of developing UC, compared to individuals who were not exposed to secondhand smoke and had low urinary total arsenic levels. Ever smokers who had been exposed to secondhand smoke and had a high urinary total arsenic level had the greatest increased risk for developing UC (10.82-fold greater). Conclusion: Individuals in a Taiwanese population who smoked cigarettes, were exposed to secondhand smoke, and a high urinary total arsenic level, had a significant risk for developing UC

TBK1-associated Protein in Endolysosomes (TAPE) Is an Innate Immune Regulator Modulating the TLR3 and TLR4 Signaling Pathways*

The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways. We found that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-β and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-β induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-β. TAPE knockdown failed to block Trif-mediated IFN-β induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-β induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step