Transcriptional Regulator TonEBP Mediates Oxidative Damages in Ischemic Kidney Injury

TonEBP (tonicity-responsive enhancer binding protein) is a transcriptional regulator whose expression is elevated in response to various forms of stress including hyperglycemia, inflammation, and hypoxia. Here we investigated the role of TonEBP in acute kidney injury (AKI) using a line of TonEBP haplo-deficient mice subjected to bilateral renal ischemia followed by reperfusion (I/R). In the TonEBP haplo-deficient animals, induction of TonEBP, oxidative stress, inflammation, cell death, and functional injury in the kidney in response to I/R were all reduced. Analyses of renal transcriptome revealed that genes in several cellular pathways including peroxisome and mitochondrial inner membrane were suppressed in response to I/R, and the suppression was relieved in the TonEBP deficiency. Production of reactive oxygen species (ROS) and the cellular injury was reproduced in a renal epithelial cell line in response to hypoxia, ATP depletion, or hydrogen peroxide. The knockdown of TonEBP reduced ROS production and cellular injury in correlation with increased expression of the suppressed genes. The cellular injury was also blocked by inhibitors of necrosis. These results demonstrate that ischemic insult suppresses many genes involved in cellular metabolism leading to local oxidative stress by way of TonEBP induction. Thus, TonEBP is a promising target to prevent AKI

Air-stable van der Waals PtTe2 conductors with high current-carrying capacity and strong spin- orbit interaction

High-performance van der Waals (vdW) integrated electronics and spintronics require reliable current-carrying capacity. However, it is challenging to achieve high current density and air-stable performance using vdW metals owing to the fast electrical breakdown triggered by defects or oxidation. Here, we report that spin-orbit interacted synthetic PtTe2 layers exhibit significant electrical reliability and robustness in ambient air. The 4-nm-thick PtTe2 synthesized at a low temperature (similar to 400 degrees C) shows intrinsic metallic transport behavior and a weak antilocalization effect attributed to the strong spin-orbit scattering. Remarkably, PtTe2 sustains a high current density approaching approximate to 31.5 MA cm(-2), which is the highest value among electrical interconnect candidates under oxygen exposure. Electrical failure is caused by the Joule heating of PtTe2 rather than defect-induced electromigration, which was achievable by the native TeOx passivation. The high-quality growth of PtTe2 and the investigation of its transport behaviors lay out essential foundations for the development of emerging vdW spin-orbitronics

Efficient pathway enrichment and network analysis of GWAS summary data using GSA-SNP2

Pathway-based analysis in genome-wide association study (GWAS) is being widely used to uncover novel multi-genic functional associations. Many of these pathway-based methods have been used to test the enrichment of the associated genes in the pathways, but exhibited low powers and were highly affected by free parameters. We present the novel method and software GSA-SNP2 for pathway enrichment analysis of GWAS P-value data. GSA-SNP2 provides high power, decent type I error control and fast computation by incorporating the random set model and SNP-count adjusted gene score. In a comparative study using simulated and real GWAS data, GSA-SNP2 exhibited high power and best prioritized gold standard positive pathways compared with six existing enrichment-based methods and two self-contained methods (alternative pathway analysis approach). Based on these results, the difference between pathway analysis approaches was investigated and the effects of the gene correlation structures on the pathway enrichment analysis were also discussed. In addition, GSA-SNP2 is able to visualize protein interaction networks within and across the significant pathways so that the user can prioritize the core subnetworks for further studies. GSA-SNP2 is freely available at https://sourceforge.net/projects/gsasnp2

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

What Makes Employees Behave Innovatively? Empirical Evidence from South Korea

Although the value of a supportive organizational strategy has been recognized over time, there is a need to better understand its relationship with employees’ psychological and behavioral responses. This study focuses on employees’ innovative behavior as a result of their perceptions of internal market orientation in the organization. It proposes a sequential process model that examines the impact of internal market orientation on employees’ innovative behavior through the ethical climate, psychological ownership, and employee stewardship toward the organization. Using data collected from 310 employees of small and medium-sized enterprises in various industries in South Korea, a linear sequential relationship among the constructs is confirmed. The findings of this empirical study, therefore, suggest that the ethical climate, psychological ownership, and stewardship mediate the effects of internal market orientation on employees’ innovative behavior. The research thus offers a conceptual framework that shows the sequential process of the effect of internal market orientation on innovative behavior. Further, it shows that the perception of an ethical climate can be influenced by management and can develop an employee’s psychological ownership. Implications for managers and directions for future research are also discussed

What Makes Employees Behave Innovatively? Empirical Evidence from South Korea

Although the value of a supportive organizational strategy has been recognized over time, there is a need to better understand its relationship with employees’ psychological and behavioral responses. This study focuses on employees’ innovative behavior as a result of their perceptions of internal market orientation in the organization. It proposes a sequential process model that examines the impact of internal market orientation on employees’ innovative behavior through the ethical climate, psychological ownership, and employee stewardship toward the organization. Using data collected from 310 employees of small and medium-sized enterprises in various industries in South Korea, a linear sequential relationship among the constructs is confirmed. The findings of this empirical study, therefore, suggest that the ethical climate, psychological ownership, and stewardship mediate the effects of internal market orientation on employees’ innovative behavior. The research thus offers a conceptual framework that shows the sequential process of the effect of internal market orientation on innovative behavior. Further, it shows that the perception of an ethical climate can be influenced by management and can develop an employee’s psychological ownership. Implications for managers and directions for future research are also discussed

An Optimal Management Strategy of Carbon Forestry with a Stochastic Price

An analysis for the value of carbon forestry needs to be provided for the successful establishment of the carbon offset market in Korea. We present an optimal management strategy for a forest owner who participates in the offset market. Given a stochastic process of the timber price following a geometric Brownian motion, the profit maximization problem of the forest owner is solved. The model finds an optimal harvest time in the presence of the carbon and timber revenues with opposing time effects. Sensitivity analysis is performed with respect to the volatility rate of the timber price and the discount rate. The presented model is applied to the study of the Korean larch case to identify the threshold timber price above which it is optimal to harvest trees

Evaluation of the Potential for Improvement of Clinical Outcomes in Trauma Patients with Massive Hemorrhage by Maintaining a High Plasma-to-Red Blood Cell Ratio during the First Hour of Hospitalization

Several reports indicate that early plasma transfusion may promote survival and reduce the incidence of traumatic coagulopathy in situations of massive bleeding. Consequently, it is recommended to maintain a plasma and RBC transfusion ratio between 1 : 1 and 1 : 2 at the start of admission. This retrospective study examined the effect of an early high plasma : RBC ratio on mortality rates by adopting a massive transfusion protocol (MTP) that forced an early and rapid issue of plasma products. Patients who received massive transfusions at a single trauma center between January 2014 and May 2020 were included in the study. A new protocol was established in January 2020, wherein a fixed amount of plasma was issued following MTP activation. Patients who underwent massive transfusions before and after the adoption of the new protocol were compared. In total, 1059 patients met the inclusion criteria. Fifty-one patients who underwent MTP were propensity score-matched with the patients who received a nonprotocolized massive transfusion. The MTP group had a higher plasma : RBC ratio at 1 h (0.8 vs. 0.2) and 4 h of hospitalization (1.1 vs. 0.6), with no significant between-group difference in the plasma : RBC ratio at 24 h of hospitalization. The MTP group had a lower 24 h mortality rate than the control group. There was no significant difference in the 30-day mortality. Using MTP to achieve a high plasma : RBC ratio in the early period of hospitalization appeared to affect 24-hour mortality; however, 30-day mortality did not change

Low Incidence of Hepatocellular Carcinoma after Antiviral Therapy in Patients with Chronic Hepatitis C and Hemophilia

Background: Hepatocellular carcinoma (HCC) rarely develops in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). We assessed the incidence of HCC in CHC patients with hemophilia after treatment with pegylated interferon plus ribavirin (PegIFN/RBV) and direct-acting antivirals (DAAs). Methods: Patients (n = 202) were enrolled between March 2007 and July 2019. A total of 139 patients were treated with PegIFN/RBV (genotype 1, n = 98; genotype 2, n = 41). Sixty-three patients were treated with DAAs (genotype 1, n = 44; genotype 2, n = 19). The cumulative incidence rates of HCC were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: For genotype 1, SVR was achieved in 78.6% (77/98) and 90.9% (40/44) of patients in the PegIFN/RBV and DAAs groups, respectively. For genotype 2, SVR was achieved in 95.1% (39/41) and 94.7% (18/19) of patients in the PegIFN/RBV and DAAs groups, respectively. Six HCC cases were identified. The cumulative incidence of HCC was 4.1% at 14 years in PegIFN/RBV and 1.7% at 5 years in DAAs. The 14-year cumulative incidence of HCC was 1.9% in the SVR group and 21.7% in the no-SVR group in the PegIFN/RBV group (p < 0.001). Conclusions: Treatment with PegIFN/RBV led to stable SVR and a low incidence of HCC. Although the follow-up period was short, DAAs led to more stable SVR than PegIFN/RBV and a low incidence of HCC in CHC patients with hemophilia