c-Jun NH2-terminal kinase activation is essential for up-regulation of LC3 during ceramide-induced autophagy in human nasopharyngeal carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Autophagy is a dynamic catabolic process characterized by the formation of double membrane vacuoles termed autophagosomes. LC3, a homologue of yeast Atg8, takes part in autophagosome formation, but the exact regulation mechanism of LC3 still needs to be elucidated.</p> <p>Methods</p> <p>Ceramide-induced autophagy was determined by detecting LC3 expression with Western blotting and confocal microscopy in human nasopharyngeal carcinoma cell lines CNE2 and SUNE1. The activation of JNK pathway was assessed by Western blotting for phospho-specific forms of JNK and c-Jun. The JNK activity specific inhibitor, SP600125, and siRNA directed against JNK were used to block JNK/c-Jun pathway. ChIP and luciferase reporter analysis were applied to determine whether c-Jun was involved in the regulation of LC3 transcription.</p> <p>Results</p> <p>Ceramide-treated cells exhibited the characteristics of autophagy and JNK pathway activation. Inhibition of JNK pathway could block the ceramide-induced autophagy and the up-regulation of LC3 expression. Transcription factor c-Jun was involved in LC3 transcription regulation in response to ceramide treatment.</p> <p>Conclusions</p> <p>Ceramide could induce autophagy in human nasopharyngeal carcinoma cells, and activation of JNK pathway was involved in ceramide-induced autophagy and LC3 expression.</p

DNA Methylation Influences Chlorogenic Acid Biosynthesis in Lonicera japonica by Mediating LjbZIP8 to Regulate Phenylalanine Ammonia-Lyase 2 Expression

The content of active compounds differ in buds and flowers of Lonicera japonica (FLJ) and L. japonica var. chinensis (rFLJ). Chlorogenic acid (CGAs) were major active compounds of L. japonica and regarded as measurements for quality evaluation. However, little is known concerning the formation of active compounds at the molecular level. We quantified the major CGAs in FLJ and rFLJ, and found the concentrations of CGAs were higher in the buds of rFLJ than those of FLJ. Further analysis of CpG methylation of CGAs biosynthesis genes showed differences between FLJ and rFLJ in the 5′-UTR of phenylalanine ammonia-lyase 2 (PAL2). We identified 11 LjbZIP proteins and 24 rLjbZIP proteins with conserved basic leucine zipper domains, subcellular localization, and electrophoretic mobility shift assay showed that the transcription factor LjbZIP8 is a nuclear-localized protein that specifically binds to the G-box element of the LjPAL2 5′-UTR. Additionally, a transactivation assay and LjbZIP8 overexpression in transgenic tobacco indicated that LjbZIP8 could function as a repressor of transcription. Finally, treatment with 5-azacytidine decreased the transcription level of LjPAL2 and CGAs content in FLJ leaves. These results raise the possibility that DNA methylation might influence the recruitment of LjbZIP8, regulating PAL2 expression level and CGAs content in L. japonica

Absolute co-supplement and absolute co-coclosed modules

A module M is called an absolute co-coclosed (absolute co-supplement) module if whenever M ≅ T/X the submodule X of T is a coclosed (supplement) submodule of T. Rings for which all modules are absolute co-coclosed (absolute co-supplement) are precisely determined. We also investigate the rings whose (finitely generated) absolute co-supplement modules are projective. We show that a commutative domain R is a Dedekind domain if and only if every submodule of an absolute co-supplement R-module is absolute co-supplement. We also prove that the class Coclosed of all short exact sequences 0→A→B→C→0 such that A is a coclosed submodule of B is a proper class and every extension of an absolute co-coclosed module by an absolute co-coclosed module is absolute co-coclosed.Scientific and Technical Research Council of Turke

Case Report: Talaromyces marneffei Infection in a Chinese Child With a Complex Heterozygous CARD9 Mutation

Talaromyces marneffei (TM) infection is rarely seen in clinical practice, and its pathogenesis may be related to deficiency in antifungal immune function. Human caspase recruitment domain-containing protein 9 (CARD9) is a key molecule in fungal immune surveillance. There have been no previous case reports of TM infection in individuals with CARD9 gene mutations. Herein, we report the case of a 7-month-old Chinese boy who was admitted to our hospital with recurring cough and fever with a papular rash. A blood culture produced TM growth, which was confirmed by metagenomic next-generation sequencing. One of the patient’s sisters had died of TM septicaemia at 9 months of age. Whole exome sequencing revealed that the patient had a complex heterozygous CARD9 gene mutation with a c.1118G&gt;C p.R373P variation in exon 8 and a c.610C&gt;T p.R204C variation in exon 4. Based on the culture results, voriconazole antifungal therapy was administered. On the third day of antifungal administration, his temperature dropped to within normal range, the rash gradually subsided, and the enlargement of his lymph nodes, liver, and spleen improved. Two months after discharge, he returned to the hospital for a follow-up examination. His general condition was good, and no specific abnormalities were detected. Oral voriconazole treatment was continued. Unexplained TM infection in HIV-negative individuals warrants investigation for immune deficiencies

Rare Copy Number Variants Identify Novel Genes in Sporadic Total Anomalous Pulmonary Vein Connection

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart anomaly. Several genes have been associated TAPVC but the mechanisms remain elusive. To search novel CNVs and candidate genes, we screened a cohort of 78 TAPVC cases and 100 healthy controls for rare copy number variants (CNVs) using whole exome sequencing (WES). Then we identified pathogenic CNVs by statistical comparisons between case and control groups. After that, we identified altogether eight pathogenic CNVs of seven candidate genes (PCSK7, RRP7A, SERHL, TARP, TTN, SERHL2, and NBPF3). All these seven genes have not been described previously to be related to TAPVC. After network analysis of these candidate genes and 27 known pathogenic genes derived from the literature and publicly database, PCSK7 and TTN were the most important genes for TAPVC than other genes. Our study provides novel candidate genes potentially related to this rare congenital birth defect (CHD) which should be further fundamentally researched and discloses the possible molecular pathogenesis of TAPVC

The Power of Transient Piezometric Head Data in Inverse Modeling: An Application of the Localized Normal-score EnKF with Covariance Inflation in a Heterogenous Bimodal Hydraulic Conductivity Field

The localized normal-score ensemble Kalman filter (NS-EnKF) coupled with covariance inflation is used to characterize the spatial variability of a channelized bimodal hydraulic conductivity field, for which the only existing prior information about conductivity is its univariate marginal distribution. We demonstrate that we can retrieve the main patterns of the reference field by assimilating a sufficient number of piezometric observations using the NS-EnKF. The possibility of characterizing the conductivity spatial variability using only piezometric head data shows the importance of accounting for these data in inverse modeling.The first author acknowledges the financial support from the China Scholarship Council (CSC). Financial support to carry out this work was also received from the Spanish Ministry of Science and Innovation through project CGL2011-23295.Xu, T.; Gómez-Hernández, JJ.; Zhou, H.; Li, L. (2013). The Power of Transient Piezometric Head Data in Inverse Modeling: An Application of the Localized Normal-score EnKF with Covariance Inflation in a Heterogenous Bimodal Hydraulic Conductivity Field. Advances in Water Resources. 54:100-118. https://doi.org/10.1016/j.advwatres.2013.01.006S1001185

Long-Term Exposure to Silica Dust and Risk of Total and Cause-Specific Mortality in Chinese Workers: A Cohort Study

A retro-prospective cohort study by Weihong Chen and colleagues provides new estimates for the risk of total and cause-specific mortality due to long-term silica dust exposure among Chinese workers

Shopping center development in China : Current situation, challenges and solutions

In recent years, shopping center becomes a more and more hot discussed topic in China due to its rapid development crossing China. The new retail format has brought both new opportunities and challenges. By comparing to western developed countries and region, China has not been involving the shopping center development for quite long time, the industry of shopping center development in China is more behind in terms of shopping center concpet development, design of a shopping center, investment model and the sysmatic professional way of shopping center development. How to lower the risks of shopping center development and have it to be a sustainable industry becomes a very crucial question to answer now. The paper will discuss those questions through literature review, interview, case study and comparison analysis. After all the research done in the paper, we can draw a few improving suggestions such as the government needs to have good commercial planning from the beginning, the developers shall have a healthy long term business model to support to have good shopping centers both for tenants and customers. Besides those, the developers should think about and use a professional way to do the shopping center development in China. The improving suggestion will need to focus on the customer needs and have long term business model

Shopping center development in China : Current situation, challenges and solutions

In recent years, shopping center becomes a more and more hot discussed topic in China due to its rapid development crossing China. The new retail format has brought both new opportunities and challenges. By comparing to western developed countries and region, China has not been involving the shopping center development for quite long time, the industry of shopping center development in China is more behind in terms of shopping center concpet development, design of a shopping center, investment model and the sysmatic professional way of shopping center development. How to lower the risks of shopping center development and have it to be a sustainable industry becomes a very crucial question to answer now. The paper will discuss those questions through literature review, interview, case study and comparison analysis. After all the research done in the paper, we can draw a few improving suggestions such as the government needs to have good commercial planning from the beginning, the developers shall have a healthy long term business model to support to have good shopping centers both for tenants and customers. Besides those, the developers should think about and use a professional way to do the shopping center development in China. The improving suggestion will need to focus on the customer needs and have long term business model