No abstract

Proteins localized to various cellular and subcellular membranes play pivotal roles in numerous cellular activities. Accordingly, in eukaryotic cells, the biogenesis of organellar proteins is an essential process requiring their correct localization among various cellular and subcellular membranes. Localization of these proteins is determined by either cotranslational or posttranslational mechanisms, depending on the final destination. However, it is not fully understood how the targeting specificity of membrane proteins is determined in plant cells. Here, we investigate the mechanism by which signal-anchored (SA) proteins are differentially targeted to the endoplasmic reticulum (ER) or endosymbiotic organelles using in vivo targeting, subcellular fractionation, and bioinformatics approaches. For targeting SA proteins to endosymbiotic organelles, the C-terminal positively charged region (CPR) flanking the transmembrane domain (TMD) is necessary but not sufficient. The hydrophobicity of the TMD in CPR-containing proteins also plays a critical role in determining targeting specificity; TMDs with a hydrophobicity value >0.4 on the Wimley and White scale are targeted primarily to the ER, whereas TMDs with lower values are targeted to endosymbiotic organelles. Based on these data, we propose that the CPR and the hydrophobicity of the TMD play a critical role in determining the targeting specificity between the ER and endosymbiotic organelles.

Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB mutations. The p.W610X mutation and large deletion were two common types of mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous without a genotype-phenotype correlation, typically manifesting cBS phenotype but also aBS or mixed Bartter-Gitelman phenotypes. The molecular diagnostic steps for patients with BS in our population should be designed taking these peculiar genotype distributions into consideration, and a new more clinically relevant classification including BS and Gitelman syndrome is required.

Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). Nonetheless, some patients are resistant to this treatment. Many efforts have been made to explain the differences in the response to steroid treatment in patients with NS based on the genetic background. We have investigated single nucleotide polymorphisms of the MDR1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and MIF (G-173C, rs755622) genes in 170 children with NS. Of these children, 69 (40.6%) were initial steroid non-responders, and 23 (13.5% of total) developed chronic kidney disease. Renal biopsy findings, which were available for 101 patients, showed that 35 patients had minimal change lesion and 66 had focal segmental glomerulosclerosis. The frequencies of the MDR1 1236 CC (18.8 vs 7.2%) or TC (53.5 vs 43.5%) genotype and C allele (45.5 vs 29.0%) were significantly higher in the initial steroid responders than in the non-responders. Analysis of MDR1 three-marker haplotypes revealed that the frequency of the TGC haplotype was significantly lower in the initial steroid responders than in the non-responders (15.8 vs 29.0%). There was no association between the MIF G-173C polymorphism and clinical parameters, renal histological findings, and steroid responsiveness. These data suggest that the initial steroid response in children with NS may be influenced by genetic variations in the MDR1 gene.

Sorafenib (SRF) is a multi-kinase inhibitor that has been shown to have antitumor activity against several types of cancers, but the effect of SRF on EBV-transformed B cells is unknown. We report that SRF can induce the apoptosis of EBV-transformed B cells through JNK/p38-MAPK activation. SRF triggered the generation of reactive oxygen species (ROS), translocation of Bax into the mitochondria, disruption of mitochondrial membrane potential, activation of caspase-9, caspase-3 and PARP, and subsequent apoptosis. Moreover, we found that SRF exposure activated the phosphorylation of JNK and p38-MAPK and suppressed the phosphorylation of PI3K-p85 and Akt. N-acetyl-l-cysteine (NAC) inhibited the activation of JNK and p38-MAPK. SP600125 and SB203580 blocked apoptosis and mitochondrial membrane disruption but did not affect ROS production after SRF treatment. These findings provide novel insights into the molecular mechanisms driving SRF-mediated cell death and suggest that SRF could be a potential therapeutic drug for the treatment of EBV-related malignant diseases.

The clinical features and prognosis of CTD-OP are similar to COP. However, lower complete recovery rate with a tendency towards higher recurrence rate in CTD-OP compared with COP suggest the need for closer follow-up in patients with CTD-OP.

Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05) by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified “cellular movement, connective tissue development and function, tissue development” and “cell-to-cell signaling and interaction, cell death and survival, cellular development” as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

Since the smartphone was first released in 2009, its common use has made everyday life convenient but caused many social problems. In this article, we surveyed the status of smartphone usage and identified the influence of smartphone addiction on mental health, campus life and personal relations of university students. We gave the methods to prevent smartphone addiction, which could be used as basic materials for solving the problems.We found the smartphone addiction syndrome cause problems of mental health, campus life and personal relations in many ways. In addition to significant direct effects, smartphone addiction has significant indirect effects on personal relations via mental health and campus life as a medium.