Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein

The XPA (Xeroderma pigmentosum A) protein is one of the six core factors of the human nucleotide excision repair system. In this study we show that XPA is a rate-limiting factor in all human cell lines tested, including a normal human fibroblast cell line. The level of XPA is controlled at the transcriptional level by the molecular circadian clock and at the post-translational level by a HECT domain family E3 ubiquitin ligase called HERC2. Stabilization of XPA by downregulation of HERC2 moderately enhances excision repair activity. Conversely, downregulation of XPA by siRNA reduces excision repair activity in proportion to the level of XPA. Ubiquitination and proteolysis of XPA are inhibited by DNA damage that promotes tight association of the protein with chromatin and its dissociation from the HERC2 E3 ligase. Finally, in agreement with a recent report, we find that XPA is post-translationally modified by acetylation. However, contrary to the previous claim, we find that in mouse liver only a small fraction of XPA is acetylated and that downregulation of SIRT1 deacetylase in two human cell lines does not affect the overall repair rate. Collectively, the data reveal that XPA is a limiting factor in excision repair and that its level is coordinately regulated by the circadian clock, the ubiquitin–proteasome system and DNA damage

Comparison of pre- and post-processors for ensemble streamflow prediction

This study conducted a broad review of the pre- and post-processor methods for ensemble streamflow prediction using a Korean case study. Categorical forecasts offered by the Korea Meteorogical Administration and deterministic forecasts of a regional climate model called Seoul National University Regional Climate Model(SNURCM) were selected as climate forecast information for the pre-processors and incorporated into Ensemble Streamflow Prediction(ESP) runs with the TANK hydrologic model. The post-processors were then used to minimize a possible error propagated through the streamflow generation. The application results show that use of the post-processor more effectively reduced the uncertainty of the no-processor ESP than use of the pre-processor, especially in dry season

Perampanel Affects Up-Stream Regulatory Signaling Pathways of GluA1 Phosphorylation in Normal and Epileptic Rats

To elucidate the pharmacological properties of perampanel [2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile, a novel non-competitive antagonist of AMPA receptor], we investigated its effects on the up-stream regulatory pathways of GluA1 phosphorylation including protein kinase C (PKC), Ca2+-calmodulin-dependent protein kinase II (CAMKII), protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), protein phosphatase (PP) 1, PP2A, and PP2B in normal and pilocarpine-induced epileptic rat model using Western blot analysis. In normal animals, perampanel affected GluA1 expression/phosphorylation, PKC, CAMKII, PKA, ERK1/2, JNK, and PPs activities. In epileptic rats, perampanel effectively inhibited spontaneous seizure activities. Perampanel enhanced phospho (p)-GluA1-S831 and -S845 ratios (phosphoprotein/total protein), while it reduced GluA1 expression. Perampanel also increased pCAMKII and pPKA ratios, which phosphorylate GluA1-S831 and -S845 site, respectively. Perampanel elevated pJNK and pPP2B ratios, which phosphorylates and dephosphorylates both GluA1-S831 and -S845 sits. Perampanel also increased pERK1/2 ratio in epileptic animals, while U0126 (an ERK1/2 inhibitor) did not affect pGluA1 ratios. Perampanel did not influence PKC, PP1, and PP2A expression levels and their phosphorylation ratios. In addition, perampanel did not have a detrimental impact on cognitive abilities of epileptic and normal rats in Morris water maze test. These findings suggest that perampanel may regulate AMPA receptor functionality via not only blockade of AMPA receptor but also the regulations of multiple molecules (CAMKII, PKA, JNK, and pPP2B)-mediated GluA1 phosphorylations without negative effects on cognition, although the effects of perampanel on PKC, PP1, and PP2A activities were different between normal and epileptic rats

Analysis of Content Legibility for Smartphones of Websites of the Korean Urological Association and Other Urological Societies in Korea

Purpose: We performed an analysis of the smartphone legibility of the websites of the Korean Urological Association (KUA) and other urological societies. Materials and Methods: This study was conducted on the websites of the KUA and nine other urological societies. Each website was accessed via iPhone Safari and Android Chrome, respectively, to evaluate the establishment and readability of the mobile web pages. The provision of Really Simple Syndication (RSS) feeds by the websites and whether the websites had Twitter and Facebook accounts were evaluated. In addition, a validation test on the web standards was performed by using the World Wide Web Consortium (W3C???) Markup Validation Service, and subsequently the numbers of errors and warnings that occurred were analyzed. Results: When accessed via Safari, two websites were legible, four were somewhat legible, and four were somewhat illegible. When accessed via Chrome, two websites were legible, six were somewhat legible, and two were somewhat illegible. One website provided an RSS feed and two websites managed members via separate Twitter accounts. No website supported mobile web pages. The result of the W3C??? Markup Validation test on 10 websites showed a mean error rate of 221.6 (range, 13-1,477) and a mean warning rate of 127.13 (range, 0-655). Conclusions: The smartphone legibility level of the websites of urological societies was relatively low. Improved smartphone legibility and web standard compliance of the websites of urological societies are required to keep up with the popularity of smartphones

A highly active and durable lanthanum strontium cobalt ferrite cathode for Intermediate-Temperature solid Oxide fuel cel

Solid oxide fuel cells (SOFCs) are promising techniques for high energy efficiency, fuel flexibility, and low pollutant emissions. For commercialization of SOFCs, it is required to decrease the operating temperature. At this intermediate temperature region, the cathodic polarization resistance significant due to the thermally activated oxygen reduction reaction (ORR). To compensate this, highly active cathode materials have been considered and lanthanum strontium cobalt ferrite (LSCF6428, La0.6Sr0.4Co0.2Fe0.8O3-δ) has been attracted as a cathode material for SOFCs because of its high mixed electronic and ionic conducting (MIEC) nature. However, one of the major concerns of LSCF6428 is the degradation during the long-term operation. Currently, Sr segregation has been reported as one of the major reasons for the LSCF degradation. In this study, we investigated LSCF2882 (La0.2Sr0.8Co0.8Fe0.2O3-δ) and compared with LSCF6428 as a SOFC cathode. X-ray diffraction (XRD) and Rietveld refinement were applied to analyze phase structures. By electrical conductivity relaxation (ECR) technique, Oxygen surface exchange coefficients (kchem) and chemical diffusion coefficients (Dchem) of LSCF2882 were evaluated and we observed enhancements compare to LSCF6428. For interpretation of enhanced oxygen transport kinetics, we tried to visualize the interstitial oxygen conduction pathways and the bond valence sum (BVS) mapping method was utilized by Valence program. BVS mapping results show clearly demonstrating the 3D network of the interstitial pathways at 600oC in LSCF2882. Electrochemical performances were investigated by EIS (Electrochemical Impedance Spectroscopy) and single cell performance was also evaluated. In addition, long-term stability test was performed for over 500 hours. LSCF2882 showed better performances and it exhibited no degradation during the stability test. Please click Additional Files below to see the full abstract

A highly active and redox stable novel ceramic anode with in-situ exsolution of nanocatalysts

Layered perovskite novel ceramic anode (referred to as SGNM) phases were evaluated for use in solid oxide fuel cells (SOFCs). Hydrogen temperature programmed reduction (H2-TPR) analysis of the SGNM materials revealed that significant exsolution of Ni nanoparticles occurred. Consistently, the SGNM on the LSGM electrolyte showed low electrode polarization resistance in H2 at 800 °C. Moreover, after 10 redox cycles at 750 °C, the electrode area specific resistance of the SGNM anode in H2 slightly increased during cycle, indicating excellent redox stability in both reducing and oxidizing atmospheres. An LSGM-electrolyte supported SOFC employing an SGNM-based anode yielded a high power density of ~1 W cm-2 at 800 °C, which is the best performance among the any SOFCs with Ruddlesden-Popper based ceramic anodes to date. After performance measurement, we observed that metallic Ni nanoparticles (~ 25 nm) were grown in situ and homogeneously distributed on the SGNM anode surface. These exsolved nanocatalysts are believed to significantly enhance the hydrogen oxidation activity of the SGNM material. These results demonstrate that the novel SGNM material is promising as a high catalytically active and redox-stable anode for SOFCs.. Please click Additional Files below to see the full abstract

Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models

<p>Abstract</p> <p>Background</p> <p>In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.</p> <p>Results</p> <p>Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.</p> <p>Conclusion</p> <p>Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.</p