A marker tephra bed close to the Lower-Middle Pleistocene boundary: Distribution of the Ontake-Byakubi Tephra Bed in central Japan

Tephrochronology is an exceptionally important tool in the precise regional correlation of Early and Middle Pleistocene sedimentary strata in Japan. The present study reveals that the Yukawa tephra 5 (YUT5) derived from the Older Ontake volcano, the Nezumigawa (Nzg) and Mitamitajima (Mtj) tephras of the Ina Bazin, and the Byakubi-E tephra (Byk-E) of the Boso Peninsula are the same tephra on the basis of their lithofacies, bulk grain composition, mafic mineral composition, major element composition of hornblende, and stratigraphic relationships with the dated tephras. We propose to call the series of tephras correlated with Byk-E the Ontake-Byakubi Tephra Bed (On-Byk Tephra) following the naming convention in which the tephra name consists of the names of the source volcano and the type location. The Matuyama-Brunhes Chronozone boundary occurs just above Byk-E in the type section of the Kokumoto Formation in the Kazusa Group, which is a candidate Global Boundary Stratotype Section and Point (GSSP) for the lower boundary of the Middle Pleistocene Subseries. Therefore, On-Byk Tephra becomes a critically important marker tephra bed for the Early-Middle Pleistocene boundary in central Japan. The present study indicates that the major element composition of hornblende can be a useful tool for identification and correlation of strongly weathered tephra layers such as Nzg and Mtj in which all the volcanic glass shards have been altered.ArticleQuaternary International. 397: 27-38(2016)journal articl

Reconstruction of the 2014 eruption sequence of Ontake Volcano from recorded images and interviews

A phreatic eruption at Mount Ontake (3067 m) on September 27, 2014, led to 64 casualties, including missing people. In this paper, we clarify the eruption sequence of the 2014 eruption from recorded images (photographs and videos obtained by climbers) and interviews with mountain guides and workers in mountain huts. The onset of eruption was sudden, without any clear precursory surface phenomena (such as ground rumbling or strong smell of sulfide). Our data indicate that the eruption sequence can be divided into three phases. Phase 1: The eruption started with dry pyroclastic density currents (PDCs) caused by ash column collapse. The PDCs flowed down 2.5 km SW and 2 km NW from the craters. In addition, PDCs moved horizontally by approximately 1.5 km toward N and E beyond summit ridges. The temperature of PDCs at the summit area partially exceeded 100 °C, and an analysis of interview results suggested that the temperature of PDCs was mostly in the range of 30–100 °C. At the summit area, there were violent falling ballistic rocks. Phase 2: When the outflow of PDCs stopped, the altitude of the eruption column increased; tephra with muddy rain started to fall; and ambient air temperature decreased. Falling ballistic rocks were almost absent during this phase. Phase 3: Finally, muddy hot water flowed out from the craters. These models reconstructed from observations are consistent with the phreatic eruption models and typical eruption sequences recorded at similar volcanoes.ArticleEarth, Planets and Space. 68:79 (2016)journal articl

Reconstruction of a phreatic eruption on 27 September 2014 at Ontake volcano, central Japan, based on proximal pyroclastic density current and fallout deposits

The phreatic eruption at Ontake volcano on 27 September 2014, which caused the worst volcanic disaster in the past half-century in Japan, was reconstructed based on observations of the proximal pyroclastic density current (PDC) and fallout deposits. Witness observations were also used to clarify the eruption process. The deposits are divided into three major depositional units (Units A, B, and C) which are characterized by massive, extremely poorly sorted, and multimodal grain-size distribution with 30–50 wt% of fine ash (silt–clay component). The depositional condition was initially dry but eventually changed to wet. Unit A originated from gravity-driven turbulent PDCs in the relatively dry, vent-opening phase. Unit B was then produced mainly by fallout from a vigorous moist plume during vent development. Unit C was derived from wet ash fall in the declining stage. Ballistic ejecta continuously occurred during vent opening and development. As observed in the finest population of the grain-size distribution, aggregate particles were formed throughout the eruption, and the effect of water in the plume on the aggregation increased with time and distance. Based on the deposit thickness, duration, and grain-size data, and by applying a scaling analysis using a depth-averaged model of turbulent gravity currents, the particle concentration and initial flow speed of the PDC at the summit area were estimated as 2 × 10−4–2 × 10−3 and 24–28 m/s, respectively. The tephra thinning trend in the proximal area shows a steeper slope than in similar-sized magmatic eruptions, indicating a large tephra volume deposited over a short distance owing to the wet dispersal conditions. The Ontake eruption provided an opportunity to examine the deposits from a phreatic eruption with a complex eruption sequence that reflects the effect of external water on the eruption dynamics.ArticleEarth, Planets and Space. 68: 82(2016)journal articl

Biochemical reconstitution of abasic DNA lesion replication in Xenopus extracts

Cellular DNA is under constant attack from numerous exogenous and endogenous agents. The resulting DNA lesions, if not repaired timely, could stall DNA replication, leading to genome instability. To better understand the mechanism of DNA lesion replication at the biochemical level, we have attempted to reconstitute this process in Xenopus egg extracts, the only eukaryotic in vitro system that relies solely on cellular proteins for DNA replication. By using a plasmid DNA that carries a site-specific apurinic/apyrimidinic (AP) lesion as template, we have found that DNA replication is stalled one nucleotide before the lesion. The stalling is temporary and the lesion is eventually replicated by both an error-prone mechanism and an error-free mechanism. This is the first biochemical system that recapitulates efficiently and faithfully all major aspects of DNA lesion replication. It has provided the first direct evidence for the existence of an error-free lesion replication mechanism and also demonstrated that the error-prone mechanism is a major contributor to lesion replication

Paleoclimatic and paleoceanographic records through Marine Isotope Stage 19 at the Chiba composite section, central Japan: A key reference for the EarlyeMiddle Pleistocene Subseries boundary

Marine Isotope Stage (MIS) 19 is an important analogue for the present interglacial because of its similar orbital configuration, especially the phasing of the obliquity maximum to precession minimum. However, sedimentary records suitable for capturing both terrestrial and marine environmental changes are limited, and thus the climatic forcing mechanisms for MIS 19 are still largely unknown. The Chiba composite section, east-central Japanese archipelago, is a continuous and expanded marine sedimentary succession well suited to capture terrestrial and marine environmental changes through MIS 19. In this study, a detailed oxygen isotope chronology is established from late MIS 20 to early MIS 18, supported by a U-Pb zircon age and the presence of the Matuyama–Brunhes boundary. New pollen, marine microfossil, and planktonic foraminiferal δ18O and Mg/Ca paleotemperature records reveal the complex interplay of climatic influences. Our pollen data suggest that the duration of full interglacial conditions during MIS 19 extends from 785.0 to 775.1 ka (9.9 kyr), which offers an important natural baseline in predicting the duration of the present interglacial. A Younger Dryas-type cooling event is present during Termination IX, suggesting that such events are linked to this orbital configuration. Millennial- to multi-millennial-scale variations in our δ18O and Mg/Ca records imply that the Subarctic Front fluctuated in the northwestern Pacific Ocean during late MIS 19, probably in response to East Asian winter monsoon variability. The climatic setting at this time appears to be related to less severe summer insolation minima at 65˚N and/or high winter insolation at 50˚N. Our records do not support a recently hypothesized direct coupling between variations in the geomagnetic field intensity and global/regional climate change. Our highly resolved paleoclimatic and paleoceanographic records, coupled with a well-defined Matuyama–Brunhes boundary (772.9 ka; duration 1.9 kyr), establish the Chiba composite section as an exceptional climatic and chronological reference section for the Early–Middle Pleistocene boundary.ArticleQuaternary Science Reviews 191: 406-430(2018)journal articl

Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia

Objectives: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19. Methods: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2). Results: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group. Conclusion: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group

糖尿病誘発性慢性腎疾患モデル動物―尿細管障害バイオマーカーによる検討―

Diabetes-induced chronic kidney disease（ DCKD） is a serious health problem. Therefore, modalities for preventing/improving DCKD are required. The aim of this study was to establish an animal model of DCKD. Four five-week-old male OLETF and LETO rats were used as experimental and control animals, respectively. After both rats were raised 17 months, collections of urine, blood and bilateral kidneys were performed. Urinary biomarkers for renal proximal tubule injury, monocyte chemoattractant protein-1（ MCP-1） and kidney injury molecule-1（ KIM-1）, were measured by the Bio-Plex system. OLETF rats showed a significant increase in blood glucose, Hb A1c, creatinine, blood urea nitrogen（ BUN）, kidney/body weight ratio, glomerular area, 24 h-urine volume, urinary protein concentrations, MCP-1 and KIM-1 compared with LETO rats. There was a positive correlation not only between BUN and MCP-1 or KIM-1 but also between urinary protein concentrations and MCP-1 or KIM-1. These results indicate that the present OLETF rats have both glomerular and proximal tubular injury. Thus, the aged male OLETF rats with long-term diabetes may become a potent animal model for examining effects of exercise/dietary therapies on DCKD

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis

<p>Abstract</p> <p>Background</p> <p>Hepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors.</p> <p>Methods</p> <p>Eighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis.</p> <p>Results</p> <p>The overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly.</p> <p>Conclusions</p> <p>Optimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.</p

A liver-derived secretory protein, selenoprotein P, causes insulin resistance

金沢大学医薬保健研究域医学系The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secretory proteins, termed hepatokines. Here, we demonstrate that selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance. Using serial analysis of gene expression (SAGE) and DNA chip methods, we found that hepatic SeP mRNA levels correlated with insulin resistance in humans. Administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes. Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice. The metabolic actions of SeP were mediated, at least partly, by inactivation of adenosine monophosphate-activated protein kinase (AMPK). In summary, these results demonstrate a role of SeP in the regulation of glucose metabolism and insulin sensitivity and suggest that SeP may be a therapeutic target for type 2 diabetes. © 2010 Elsevier Inc