TRIP13 Participates in Immediate-Early Sensing of DNA Strand Breaks and ATM Signaling Amplification through MRE11

Thyroid hormone receptor-interacting protein 13 (TRIP13) participates in various regulatory steps related to the cell cycle, such as the mitotic spindle assembly checkpoint and meiotic recombination, possibly by interacting with members of the HORMA domain protein family. Recently, it was reported that TRIP13 could regulate the choice of the DNA repair pathway, i.e., homologous recombination (HR) or nonhomologous end-joining (NHEJ). However, TRIP13 is recruited to DNA damage sites within a few seconds after damage and may therefore have another function in DNA repair other than regulation of the pathway choice. Furthermore, the depletion of TRIP13 inhibited both HR and NHEJ, suggesting that TRIP13 plays other roles besides regulation of choice between HR and NHEJ. To explore the unidentified functions of TRIP13 in the DNA damage response, we investigated its genome-wide interaction partners in the context of DNA damage using quantitative proteomics with proximity labeling. We identified MRE11 as a novel interacting partner of TRIP13. TRIP13 controlled the recruitment of MDC1 to DNA damage sites by regulating the interaction between MDC1 and the MRN complex. Consistently, TRIP13 was involved in ATM signaling amplification. Our study provides new insight into the function of TRIP13 in immediate-early DNA damage sensing and ATM signaling activation

Whole-genome, transcriptome, and methylome analyses provide insights into the evolution of platycoside biosynthesis in Platycodon grandiflorus, a medicinal plant

Triterpenoid saponins (TSs) are common plant defense phytochemicals with potential pharmaceutical properties. Platycodon grandiflorus (Campanulaceae) has been traditionally used to treat bronchitis and asthma in East Asia. The oleanane-type TSs, platycosides, are a major component of the P. grandiflorus root extract. Recent studies show that platycosides exhibit anti-inflammatory, antiobesity, anticancer, antiviral, and antiallergy properties. However, the evolutionary history of platycoside biosynthesis genes remains unknown. In this study, we sequenced the genome of P. grandiflorus and investigated the genes involved in platycoside biosynthesis. The draft genome of P. grandiflorus is 680.1Mb long and contains 40,017 protein-coding genes. Genomic analysis revealed that the CYP716 family genes play a major role in platycoside oxidation. The CYP716 gene family of P. grandiflorus was much larger than that of other Asterid species. Orthologous gene annotation also revealed the expansion of beta -amyrin synthases (bASs) in P. grandiflorus, which was confirmed by tissue-specific gene expression. In these expanded gene families, we identified key genes showing preferential expression in roots and association with platycoside biosynthesis. In addition, whole-genome bisulfite sequencing showed that CYP716 and bAS genes are hypomethylated in P. grandiflorus, suggesting that epigenetic modification of these two gene families affects platycoside biosynthesis. Thus whole-genome, transcriptome, and methylome data of P. grandiflorus provide novel insights into the regulation of platycoside biosynthesis by CYP716 and bAS gene families

Factors leading to slope failure on a sediment-starved margin: The southwestern continental margin of the East Sea, Korea

21 pages, 16 figures, 2 tablesSubmarine landslides are common geomorphological features of continental margins. Some of the largest submarine landslides occurred on low-angle (< 4°), sediment-starved margins, yet their preconditioning and trigger mechanisms are still largely unconstrained. The southwestern continental margin of the East Sea (between 37.5°N and 38.0°N), Korea, occupies a narrow shelf (< 10 km), is characterized by low sedimentation rates (~3–7 cm /ka) with an average gradient of less than 2°. Here, we investigate submarine landslides using newly collected datasets including multibeam echosounder (MBES), chirp sub-bottom profiler, multichannel seismic (MCS) data and ten piston cores. MBES data from the margin reveal at least four major submarine landslides initiated at depths of 400 m to over 600 m. These landslides left clear headwall scarps on the seafloor with reliefs reaching over ~130 m and extend for over 40 km. MCS data show that some of the failures have resulted in the complete disintegration of the failed mass, while others have resulted in the deposition of well-defined hummocky debris flows. Sediments recovered downslope of the headwall scarps contain slides and debris flow deposits and turbidites that are overlain by bioturbated hemipelagic layers. Radiocarbon dating from hemipelagic units overlying MTDs within the headwall scarps reveal that major failures occurred at ca. 11 to 19 ka, coinciding with the time of the Last Glacial Maximum (LGM) to early deglaciation. Since then, hemipelagic sedimentation has prevailed throughout the sediment starved slope. Slope stability analyses based on geotechnical properties of sediments indicate that all areas are stable under static, and even stable under loads derived from earthquakes in instrumental records, but there were probably earthquakes in pre-historical records (i.e., with a longer recurrence interval) of potentially significant larger magnitude. We suggest that the preferential occurrence of major failures adjacent to the major faults on the lower slope may ultimately be tectonic-controlled although other factors may have contributed as well. Our work shows that coarse-grained clastic sediments are abundant in the shallow subsurface and that these higher-permeability units, often identified as weak layers, would focus fluid flow and could act as slip planes for slope failure. Our data also indicate that tectonic steepening and gas charging are other key parameters for controlling instability in sediment-starved marginsThis study was supported by the project entitled “Geological survey in the Korean Peninsula and publication of the geological maps (GP2020-009)” of the Korea Institute of Geoscience and Mineral Resources (KIGAM) funded by the Ministry of Science and ICT. The Spanish “Ministerio de Ciencia e Innovación” and the European Regional Development Fund through grant CTM2015-70155-R (project INSIGHT) are also acknowledgedWith the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)Peer reviewe

Factors for pre-conditioning and post-failure behaviour of submarine landslides in the margins of Ulleung Basin, East Sea (Japan Sea)

Glide planes, the basal surface or failure surface upon which submarine landslides initiate, commonly develop along weak, distinctive stratigraphic horizons but their lithological/mechanical characteristics and genetic mechanisms remain largely unknown. We use 2-D multi-channel seismic reflection data, integrated with multibeam bathymetry and deep drilling data from the Ulleung Basin margins, East (Japan) Sea, to: (1) identify and characterize the nature of glide planes associated with submarine landslides; (2) understand the influence of climate-modulated factors in preconditioning slope failures; and (3) document the post-failure evolution of the landslides. 24 glide planes were identified among 38 submarine slides (SL1 – SL38), which correspond to regionally continuous, positive-polarity high-amplitude seismic reflections. Well-seismic integration support ca. 340 ka – 1,200 ka ages of formation of the major glide planes in the southwestern and western margins of the basin. These glide planes developed at the interface between clay-rich sediment deposited during glacial periods and biogenic diatom-rich sediments deposited during interglacial periods. Physical, mineralogical and geochemical properties determined by density, porosity, gamma-ray, shear strength, X-ray diffraction, and X-ray fluorescence data reveal significant lithological and mechanical changes at the interface between these two lithologies. We therefore infer that these interfaces dictate the position of failure surfaces, with the diatom-rich layers acting as a weak layer. Excess pore pressure in these layers is likely due to initial high-water contents (up to 75%) and high compressibility; this is considered an important pre-condition for failure. In contrast, the glide planes along the northwestern margin of the Ulleung Basin (SL34 – 37) are older (ca. 1,200 ka – 2,140 ka). Seismic data further reveal three distinct contrasting styles of landslide post-failure behavior throughout the margins: (1) evacuated slide scars with areas of smooth seafloor; (2) slide scars with residual debris consisting of blocky sediments; and (3) slide scars with buried intact sediment blocks in front of the headwalls. Lateral variability of fluid flow, sediment composition, and mechanical properties of basal ‘weak’ layer(s), or the magnitude of earthquakes may have contributed to forming different types of mass-transport deposits (MTDs). Overall, these results show that landslide formation in the East (Japan) Sea result from a complex climatic, volcanic and tectonic interplay that controlled the formation of weak layers. Some of these layers extend regionally and can be identified and mapped by remote geophysical methods and targeted drilling

Tsunami hazard from submarine landslides: scenario-based assessment in the Ulleung Basin, East Sea (Japan Sea)

22 pages, 20 figures, 1 tableIn this study we use a scenario-based approach to highlight potential tsunami hazard from actual Late Pleistocene submarine landslides in the Ulleung Basin: two submarine landslides on the western slope of the Ulleung Basin, north and south of the Hupo Bank (2.53 and 1.12 km3 respectively) and a landslide (15.1 km3) on the continental slope south of the Ulleung Basin. The simulations attempt to highlight the consequences, should one of these events occur at Present. Results of the simulations indicate potential local hazard zones with very local waves 3 m in the stretch of coastline from Ulsan in the south to Uljin in the north. The timing available for early warning from landslide tsunamis originating in this area is 15–30 minutes along the affected section of the shoreline. We also suggest a Probabilistic Tsunami Hazard Assessment (PTHA) for comprehensive assessments of the Korean coast of the East Sea. PTHA accounts for uncertainties in location, release mechanisms, evolution, and return periods of submarine landslides as well as epistemic uncertainty. However, to constrain these uncertainties detailed information on source areas, recurrence period and dynamics of submarine landslides is necessary and calls for additional data collection and further studiesThis research is a contribution to KIGAM’s projects “Developmentof Integrated Geological Information Based on Digital Mapping”(GP2017-021) and “Evaluation of seismic active faults andpossibility of submarine earthquakes in the southern part of the East Sea, Korea” (NP2018-18). The Spanish “Ministerio de Economia y Competitividad” and the European Regional Development Fund through grant CTM2015-70155-R (project INSIGHT) are also acknowledged. This study is also supportedby research fund of Chungnam National University and KIOST Basic Project (PE99646)Peer Reviewe

전단접착강도와 관련된 Plasma Arc Curing Light의 중합효율평가

The objective of this study was to compare dentin shear bond strength (DSBS) of dentin bonding agents (DBAs) cured with a plasma arc (PAC) light curing unit (LCU) and those cured with a light emitting diode (LED) LCU. Optical properties were also analyzed for Elipar freelight 2 (3M ESPE); LED LCU, Apollo 95E (DMT Systems); PAC LCU and VIP Junior (Bisco); Halogen LCU. The DBAs used for DSBS test were Scotchbond Multipurpose (3M ESPE), Singlebond 2 (3M ESPE) and Clearfil SE Bond (Kuraray). After DSBS testing, fractured specimens were analyzed for failure modes with SEM. The total irradiance and irradiance between 450 ㎚ and 490 ㎚ of the LCUs were different. LED LCU showed narrow spectral distribution around its peak at 462 ㎚ whereas PAC and Halogen LCU showed a broad spectrum. There were no significant differences in mean shear bond strength among different LCUs (P > 0.05) but were significant differences among different DBAs (P < 0.001). 광물리학적 특성 분석을 위해 Apollo 95E (DMT Systems, Orange, CA; PAC 광중합기), Elipar Freelight 2 (3M ESPE, MN, USA; LED 광중합기) 그리고 VIP Junior (Bisco, Schaumberg, IL, USA; QTH 광중합기), 3종 의 광중합기의 총광강도(Total intensity)와 spectral distribution을 측정하였고 특정 파장에 해당되는 광강도 (Energy density)를 분석하였다. 상아질 전단접착강도의 측정을 위해 Scotchbond Multipurpose (3M ESPE), Single bond (3M ESPE) 그리고 Clearfil SE bond (Kuraray)가 사용되었다. Plasma Arc Curing light (Apollo 95E) 광중합기는 여러개의 최대정점을 가지며 넓은 spectral distribution과 2307 ㎽/㎠의 높은 광강도를 나타내었고, VIP Junior 광중합기는 490 ㎚에서 최대정점을 갖는 넓은 spectral distribution을 나타내었고, Elipar Freeelight 2 광중합기는 462 ㎚의 최대정점 주위로 좁은 spectral distribution을 보였 다. Two-Way ANOVA와 Bonferronis multiple comparison test를 이용하여 상아질 전단접착강도를 분석한 결과, PAC 광중합기와 LED 광중합기 간에 유의성 있는 차이를 보이지 않았으며 (P > 0.05), 상아질 접착제와 광중합기의 교호관계에도 유의성이 없었다. 그러나 상아질 접착제는 상호간에 유의성 있는 차이를 보였다 (P < 0.001).This study was supported by SNUH FUND 04-2006-0007

JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells

The objective of this study was to determine whether (5S)-5-(4-benzyloxy-3,5-dimethoxy-phenyl)-5,9-dihydro-8H-furo [3&rsquo;,4&rsquo;:6,7] naphtho [2,3-d] [1,3]dioxol-6-one (JNC-1043), which is a novel chemical derivative of &beta;-apopicropodophyllin, acts as a novel potential anticancer reagent and radiosensitizer in colorectal cancer (CRC) cells. Firstly, we used MTT assays to assess whether JNC-1043 could inhibit the cell proliferation of HCT116 and DLD-1 cells. The IC50 values of these cell lines were calculated as 114.5 and 157 nM, respectively, at 72 h of treatment. Using doses approximating the IC50 values, we tested whether JNC-1043 had a radiosensitizing effect in the CRC cell lines. Clonogenic assays revealed that the dose-enhancement ratios (DER) of HCT116 and DLD-1 cells were 1.53 and 1.25, respectively. Cell-counting assays showed that the combination of JNC-1043 and &gamma;-ionizing radiation (IR) enhanced cell death. Treatment with JNC-1043 or IR alone induced cell death by 50~60%, whereas the combination of JNC-1043 and IR increased this cell death by more than 20~30%. Annexin V-propidium iodide assays showed that the combination of JNC-1043 and IR increased apoptosis by more 30~40% compared to that induced by JNC-1043 or IR alone. DCFDA- and MitoSOX-based assays revealed that mitochondrial ROS production was enhanced by the combination of JNC-1043 and IR. Finally, we found that suppression of ROS by N-acetylcysteine (NAC) blocked the apoptotic cell death induced by the combination of JNC-1043 and IR. The xenograft model also indicated that the combination of JNC-1043 and IR increased apoptotic cell death in tumor mass. These results collectively suggest that JNC-1043 acts as a radiosensitizer and exerts anticancer effects against CRC cells by promoting apoptosis mediated by mitochondrial ROS

The effect of cavity wall property on the shear bond strength test using iris method

Objectives : In the unique metal iris method. the developing interfacial gap at the cavity floor resulting from the cavity wall property during polymerizing composite resin might affect the nominal shear bond strength values. The aim of this study is to evaluate that the iris method reduces the cohesive failure in the substrates and the cavity wall property effects on the shear bond strength tests using iris method. Materials and Methods : The occlusal dentin of 64 extracted human molars were randomly divided into 4 groups to simulate two different levels of cavity wall property (metal and dentin iris) and two different materials ( and 2) for each wall property. After positioning the iris on the dentin surface. composite resin was packed and light-cured. After 24 hours the shear bond strength was measured at a crosshead speed of 0.5 mm/min. Fracture analysis was performed using a microscope and SEM. The data was analyzed statistically by a two-way ANOV A and t-test. Results : The shear bond strength with metal iris was significant higher than those with dentin iris (p＝0.034). Using , the shear bond strength with metal iris was significant higher than those with dentin iris (p＝0.005), but not in 2 (p＝0.774). The incidence of cohesive failure was very lower than other shear bond strength tests that did not use iris method. Conclusions：The iris method may significantly reduce the cohesive failures in the substrates. According to the bonding agent systems. the shear bond strength was affected by the cavity wall property.This work was supported by a grant from the Ministry of Health and Welfare of Korea (Grant No. 03 PJ1 PG1 CH09 0001) and in part by the Korea Science and Engineering Foundation through the Intellectual Biointerface Engineering Center at Seoul National University

Submarine landslides on the Eastern South Korea Plateau (ESKP) - Do pumice-rich tephra layers control slope stability?

Tephra layers embedded in marine sediments can be significant in controlling submarine landslide dynamics and seafloor morphology, but their preconditioning effects on slope failure remain uncertain. Here, we study the morphology and preconditioning factors of submarine landslides from a volcanically active region, the Eastern South Korea Plateau (ESKP) using a recently acquired multibeam echosounder (MBES), high-resolution sub-bottom chirp profiler, and piston core data, together with previous geophysical data. At least 50 translational landslides were identified on the southern margin of the ESKP in an area of ∼470 km2, with a relatively small volume of remobilized sediment (∼10 km3). The landslide headscarps are arcuate, up to 400 m in height, and lie at water depths of 980 to 2300 m. Landslides on the upper ESKP margin are more disintegrative (debris flow type) than those on the lower margin which consists largely of blocky type failures with small runouts. Landslide deposits identified in the cores consist of debris flows and slides/slumps while background deposits contain hemipelagic mud interbedded with ca. 10-cm-thick coarse-grained, poorly-sorted pumiceous tephra. Seismic and core integration indicate that the glide planes of the observed slides correspond to the pumice-rich tephra layers. These tephras are predominantly composed of fresh volcanic glass devoid of clay, indicating that the composition of the tephra did not control the formation of weak layers or slide planes. We infer therefore that the weakness of the glide planes resulted from high hydraulic (pore) pressure at the interface between some of the porous tephra layers and their overlying, relatively impermeable, hemipelagic mud. In addition to burial compaction and build-up of pore pressure in the tephra layers, fluid overpressure could have been facilitated by earthquakes causing granular convection within, and compaction of, the poorly sorted tephra. The landslide predominantly formed > ca. 84 ka ago, which suggests time-restricted triggering associated with a temporary increase in seismicity and/or sediments reaching their overpressure threshold during burial compaction. Our study suggests that regional occurrences of discrete layers of porous tephra deposits within finer grained hemipelagic sediments can potentially control the generation of landslides in subaqueous environments affected by explosive volcanism