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

Plastomes of Sonchus (Asteraceae) endemic to the Atlantic Madeira archipelago: Genome structure, comparative analysis, and phylogenetic relationships

The woody Sonchus alliance, a spectacular example of adaptive radiation with six genera and approximately 31 species, is found exclusively on three Macaronesian Islands (Madeira, Canaries, and Cape Verdes) in the Atlantic Ocean. Four of the Sonchus taxa are restricted to Madeira, including shrubs and small trees at higher elevations (S. fruticosus and S. pinnatus), and caudex perennials in the lower coastal areas (S. ustulatus subsp. maderensis and S. ustulatus subsp. ustulatus). The Madeiran Sonchus stemmed from a single colonization event that originated from the Canaries < 3 million years ago. However, the plastome evolution and species relationships remains insufficiently explored. We therefore assembled and characterized the plastomes of four Sonchus taxa from Madeira and conducted a phylogenomic analysis. We found highly conserved plastome sequences among the taxa, further supporting a single and recent origin. We also found highly conserved plastomes among the cosmopolitan weedy Sonchus, Macaronesian Sonchus in the Atlantic, and Juan Fernández Islands Dendroseris in the Pacific. Furthermore, we identified four mutation hotspot regions (trnK-rps16, petN-psbM, ndhF-Ψycf1, and ycf1) and simple sequence repeat motifs. This study strongly supports the monophyly of Madeiran Sonchus. However, its relationship with the remaining woody Sonchus alliance from the Canary Islands requires further investigation

Characterization of the complete chloroplast genome of the woody sow-thistle, Sonchus leptocephalus (Asteraceae) endemic to the Canary Islands

Sonchus leptocephalus belongs to a core member of the woody Sonchus alliance endemic to the Macaronesian Islands in the Atlantic Ocean. The alliance has been subject to intensive investigations of adaptive radiation on oceanic islands. As an attempt to fully understand the patterns and processes of evolution in this group, we determined the complete chloroplast genome of S. leptocephalus endemic to the Canaries. It was 152,406 bp in length, comprising 84,331 bp of large single copy and 18,583 bp of small single copy separated by 24,746 bp of inverted repeats. A total of 130 genes were determined including 87 protein-coding genes, 6 ribosomal RNA, and 37 transfer RNA genes. Phylogenetic analysis confirmed its position within the woody Sonchus alliance

Does whey protein supplementation during resistance exercise have additional benefits for decreasing hepatic fat content?

Background Exercise and diet have positive effects on hepatic fat reduction, and protein supplementation is known to lower hepatic fat accumulation. However, the effect of a combination of exercise and whey protein supplementation (WPS) on hepatic fat content (HFC) is unknown. Methods We investigated the effect of WPS on HFC during resistance exercise and diet control intervention for four weeks. A total of 34 sedentary males participated and were randomly assigned to two groups: a protein supplement group (PSG, n = 18) and a control group (CG, n = 16). The PSG took 60 g of WPS per day, and the CG took 60 g of an isocaloric placebo per day. All participants were fed a calorie-controlled diet throughout the study period, with their daily caloric intake determined by their resting metabolic rate and physical activity level. Both groups performed resistance exercises supervised by experts at 60–70% of their maximum efforts for 60 min/day, 6 days/week for 4 weeks. HFC was assessed using the controlled attenuation parameter (CAP) after an 8 h fast, at pre-, mid-, and post-intervention. Liver enzymes and lipid profile were also analyzed after an 8 h fast and pre- and post-intervention. Results The CAP was significantly reduced after 4 weeks of intervention in both groups (PSG, p < .001; CG, p = .002). However, there was no significant interaction between the group and changes in CAP. Interestingly, when comparing the pre- and mid-tests, both groups also had significantly reduced CAP (PSG, p = .027; CG, p = .028), but there was a significant difference in the amount of change in CAP between the two groups (PSG, -47.2 ± 25.4 dB/m; CG, -19.5 ± 15.1 dB/m; p = .042). For liver enzymes, there was a significant interaction between the two groups and a change in aspartate transaminase (AST) (p = .038). However, alanine aminotransferase (ALT) levels were significantly decreased only in the PSG group (p = .002). In lipids, both groups showed significantly decreased total cholesterol (p < .001) and low-density lipoprotein cholesterol (p < .001) after the intervention. Conclusion Our data showed that WPS may not enhance the overall effects of resistance exercise on HFC and lipid profiles. However, in part, WPS may have a beneficial effect on liver enzymatic changes and rapid response to resistance exercise-induced HFC reduction

Dendropanoxide, a Triterpenoid from <i>Dendropanax morbifera</i>, Ameliorates Hepatic Fibrosis by Inhibiting Activation of Hepatic Stellate Cells through Autophagy Inhibition

Hepatic fibrosis results from chronic liver damage and is characterized by excessive accumulation of extracellular matrix (ECM). In this study, we showed that dendropanoxide (DPX), isolated from Dendropanax morbifera, had anti-fibrotic effects on hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. DPX suppressed mRNA and protein expression of α-SMA, fibronectin, and collagen in activated HSCs. Moreover, DPX (40 mg/kg) treatment significantly lowered levels of liver injury markers (aspartate aminotransferase and alanine transaminase), expression of fibrotic markers, and deposition of ECM in a carbon tetrachloride-induced mouse model. Anti-fibrotic effects of DPX were comparable to those of silymarin in a hepatic fibrosis mouse model. As a possible mechanism of anti-fibrotic effects, we showed that DPX inhibited autophagosome formation (LC3B-II) and degradation of p62, which have important roles in HSC activation. These findings suggest that DPX inhibits HSC activation by inhibiting autophagy and can be utilized in hepatic fibrosis therapy

Influence of Supports on the Catalytic Activity and Coke Resistance of Ni Catalyst in Dry Reforming of Methane

The dependence of the catalytic activity and coke resistance of Ni-based catalysts on the support type was investigated in the dry reforming of methane (DRM). Catalysts were prepared using incipient wetness impregnation and analyzed using ICP-OES, BET-BJH, XRD, H2-chemisorption, H2-TPR, and CO2-TPD. DRM was performed at 600–750 °C at 144,000 mL/gcat∙h of GHSV (CH4/CO2/N2 = 1/1/1). Ni/Al2O3 and Ni/MgO catalysts formed NiAl2O4 and NiO-MgO solid solutions, respectively, owing to strong binding between the metal and support. In contrast, MgO-Al2O3 and MgAl2O4 supports suppressed NiAl2O4 and NiO-MgO solid solution formation, due to Mg addition, with high metal dispersions of 4.6 and 6.6%, respectively. In the DRM reaction, the Ni/MgO-Al2O3 and Ni/MgAl2O4 catalysts showed high CH4 conversions of 78.1 and 76.8%, respectively, compared with Ni/Al2O3 and Ni/MgO at 750 °C. A stability test was performed at 600 °C for 20 h. A coke study of the spent catalysts was performed using SEM and TGA. Alkaline-earth metal-containing catalysts Ni/MgO-Al2O3 and Ni/MgAl2O4 with strong CO2 adsorption properties showed 20 wt% reduction in carbon deposition compared to commercial catalysts. Therefore, the support and basic properties of the catalyst significantly influenced the catalyst performance and coke resistance in the DRM

EVI1 activates tumor-promoting transcriptional enhancers in pancreatic cancer

Cancer cells utilize epigenetic alterations to acquire autonomous capabilities for tumor maintenance. Here, we show that pancreatic ductal adenocarcinoma (PDA) cells utilize super-enhancers (SEs) to activate the transcription factor EVI1 (ecotropic viral integration site 1) gene, resulting in activation of an EVI1-dependent transcription program conferring PDA tumorigenesis. Our data indicate that SE is the vital cis-acting element to maintain aberrant EVI1 transcription in PDA cells. Consistent with disease progression and inferior survival outcomes of PDA patients, we further show that EVI1 upregulation is a major cause of aggressive tumor phenotypes. Specifically, EVI1 promotes anchorage-independent growth and motility in vitro and enhances tumor propagation in vivo. Mechanistically, EVI1-dependent activation of tumor-promoting gene expression programs through the stepwise configuration of the active enhancer chromatin attributes to these phenotypes. In sum, our findings support the premise that EVI1 is a crucial driver of oncogenic transcription programs in PDA cells. Further, we emphasize the instructive role of epigenetic aberrancy in establishing PDA tumorigenesis

Discovery of a transdermally deliverable pentapeptide for activating AdipoR1 to promote hair growth

Abstract Alopecia induced by aging or side effects of medications affects millions of people worldwide and impairs the quality of life; however, there is a limit to the current medications. Here, we identify a small transdermally deliverable 5‐mer peptide (GLYYF; P5) that activates adiponectin receptor 1 (AdipoR1) and promotes hair growth. P5 sufficiently reproduces the biological effect of adiponectin protein via AMPK signaling pathway, increasing the expression of hair growth factors in the dermal papilla cells of human hair follicle. P5 accelerates hair growth ex vivo and induces anagen hair cycle in mice in vivo. Furthermore, we elucidate a key spot for the binding between AdipoR1 and adiponectin protein using docking simulation and mutagenesis studies. This study suggests that P5 could be used as a topical peptide drug for alleviating pathological conditions, which can be improved by adiponectin protein, such as alopecia

Antioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro

Alzheimer’s disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aβ), and Aβ-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09®), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer’s disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aβ, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential