Drosophila ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle.

The function of AarF domain-containing kinase 1 (ADCK1) has not been thoroughly revealed. Here we identified that ADCK1 utilizes YME1-like 1 ATPase (YME1L1) to control optic atrophy 1 (OPA1) and inner membrane mitochondrial protein (IMMT) in regulating mitochondrial dynamics and cristae structure. We firstly observed that a serious developmental impairment occurred in Drosophila ADCK1 (dADCK1) deletion mutant, resulting in premature death before adulthood. By using temperature sensitive ubiquitously expression driver tub-Gal80ts/tub-Gal4 or muscle-specific expression driver mhc-Gal4, we observed severely defective locomotive activities and structural abnormality in the muscle along with increased mitochondrial fusion in the dADCK1 knockdown flies. Moreover, decreased mitochondrial membrane potential, ATP production and survival rate along with increased ROS and apoptosis in the flies further demonstrated that the structural abnormalities of mitochondria induced by dADCK1 knockdown led to their functional abnormalities. Consistent with the ADCK1 loss-of-function data in Drosophila, ADCK1 over-expression induced mitochondrial fission and clustering in addition to destruction of the cristae structure in Drosophila and mammalian cells. Interestingly, knockdown of YME1L1 rescued the phenotypes of ADCK1 over-expression. Furthermore, genetic epistasis from fly genetics and mammalian cell biology experiments led us to discover the interactions among IMMT, OPA1 and ADCK1. Collectively, these results established a mitochondrial signaling pathway composed of ADCK1, YME1L1, OPA1 and IMMT, which has essential roles in maintaining mitochondrial morphologies and functions in the muscle.

Vulnerabilities of Live-Streaming Services in Korea.

Recently, the number of users and the demand for live-streaming services have increased. This has exponentially increased the traffic to such services, and live-streaming service platforms in Korea use a grid computing system that distributes traffic to users and reduces traffic loads. However, ensuring security with a grid computing system is difficult because the system exchanges general user traffic in a peer-to-peer (P2P) manner instead of receiving data from an authenticated server. Therefore, in this study, to explore the vulnerabilities of a grid computing system, we investigated a vulnerability discovery framework that involves a three-step analysis process and eight detailed activities. Four types of zero-day vulnerabilities, namely video stealing, information disclosure, denial of service, and remote code execution, were derived by analyzing a live-streaming platform in Korea, as a representative service, using grid computing.

Von Hippel-Lindau tumor suppressor (VHL) stimulates TOR signaling by interacting with phosphoinositide 3-kinase (PI3K).

Cell growth is positively controlled by the phosphoinositide 3-kinase (PI3K)-target of rapamycin (TOR) signaling pathway under conditions of abundant growth factors and nutrients. To discover additional mechanisms that regulate cell growth, here we performed RNAi-based mosaic analyses in the Drosophila fat body, the primary metabolic organ in the fly. Unexpectedly, the knockdown of the Drosophila von Hippel-Lindau (VHL) gene markedly decreased cell size and body size. These cell growth phenotypes induced by VHL loss of function were recovered by activation of TOR signaling in Drosophila Consistent with the genetic interactions between VHL and the signaling components of PI3K-TOR pathway in Drosophila, we observed that VHL loss of function in mammalian cells causes decreased phosphorylation of ribosomal protein S6 kinase and Akt, which represent the main activities of this pathway. We further demonstrate that VHL activates TOR signaling by directly interacting with the p110 catalytic subunit of PI3K. On the basis of the evolutionarily conserved regulation of PI3K-TOR signaling by VHL observed here, we propose that VHL plays an important role in the regulation and maintenance of proper cell growth in metazoans.

ULK1 negatively regulates Wnt signaling by phosphorylating Dishevelled.

Wnt signaling pathway plays critical roles in body axes patterning, cell fate specification, cell proliferation, cell migration, stem cell maintenance, cancer development and etc. Deregulation of this pathway can be causative of cancer, metabolic disease and neurodegenerative disease such as Parkinson`s disease. Among the core components of Wnt signaling pathway, we discovered that Dishevelled (Dsh) interacts with ULK1 and is phosphorylated by ULK1. Unexpectedly, the knockdown of ULK1 elicited a marked increase in Wnt/ß-catenin signaling. Multiple ULK1 phosphorylation sites existed on Dsh and many of them were located on the PDZ-DEP region. By using evolutionarily well conserved Drosophila Dsh, we found that S239, S247 and S254 in the PDZ-DEP region are involved in phosphorylation of Dsh by ULK1. Among these, S247 and S254 were conserved in human Dsh. When phospho-mimetic mutants (2D and 2E Dsh mutants) of these conserved residues were generated and expressed in the eyes of the fruit flies, the activity of Dsh was significantly decreased compared to wild type Dsh. Through additional alanine scanning, we further identified that S239, S247, S254, S266, S376, S554 and S555 on full length Dsh were phosphorylated by ULK1. In regards to the S266A mutation located in the PDZ domain among these phosphorylated residues, our results suggested that Dsh forms an SDS-resistant high molecular weight complex with ß-catenin and TCF in the nucleus in an S266 phosphorylation-dependent manner. Based on these results, we propose that ULK1 plays a pivotal role in the regulation of Wnt/ß-catenin signaling pathway by phosphorylating Dsh.

A radiographic study of the posterior superior alveolar artery.

PURPOSE: The purpose of this study was to elucidate the differences of the prevalence and diameter of the posterior superior alveolar artery (PSAA) and the distance of its inferior border from the alveolar crest on computed tomography (CT) images according to age and sex. MATERIALS AND METHODS: CT images of maxilla in 200 patients were randomly selected from patients who underwent CT imaging at Yonsei University Dental Hospital, and analyzed. The prevalence of the PSAA in maxillary sinus and the distance of its inferior border from the alveolar crest in the premolar and molar area were measured. RESULTS: The average prevalence of the PSAA on CT images was 52.0%, and it is higher in males (64%) than in females (40%). The diameter of the PSAA was 1.52 ± 0.47 mm (mean ± SD), and larger in males. The distance from the PSAA to the alveolar crest was greater in the premolar area (18.90 ± 4.21 mm) than in the molar area (15.45 ± 4.04 mm), and it did not differ significantly with age or sex. CONCLUSIONS: The prevalence of the PSAA on CT images was higher, and the diameter was larger in males. The PSAA was more close to the alveolar crest in the molar areas. The evaluation of the PSAA in maxillary sinus on CT images before surgery could reduce the likelihood of excess bleeding during surgery especially in molar areas.