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Oxygen isotope ratios (δ18 O) of tree-ring cellulose are a novel proxy for summer hydroclimate in monsoonal Asia. In central Japan, we collected 67 conifer wood samples, mainly Chamaecyparis obtusa , with ages encompassing the past 2600 years. The samples were taken from living trees, archeological wood, architectural wood, and buried logs. We analyzed stable isotope ratios of oxygen (δ18 O) and hydrogen (δ2 H) in tree-ring cellulose in these samples (more than 15 000 rings in total) without using a pooling method and constructed a statistically reliable tree-ring cellulose δ18 O time series for the past 2500 years. However, there were distinct age trends and level offsets in the δ18 O record, and cellulose δ18 O values showed a gradual decrease as an individual tree matures. This suggested it is difficult to establish a cellulose δ18 O chronology for low-frequency signals by simple averaging of all the δ18 O time series data. In addition, there were opposite age trends in the cellulose δ2 H, and δ2 H gradually increased with tree age. There were clear positive correlations in the short-periodicity variations between δ18 O and δ2 H, probably indicating a common climate signal. A comparison of the δ18 O and δ2 H time series in individual trees with tree-ring width suggested that the opposite age trends of δ18 O and δ2 H are caused by temporal changes in the degree of post-photosynthetic isotope exchange with xylem water (physiological effect), accompanied by changes in stem growth rate that are influenced by human activity in the forests of central Japan. Based on the assumptions that cellulose δ18 O and δ2 H vary positively and negatively with constant proportional coefficients due to climatological and physiological effects, respectively, we solved simultaneous equations for the climatological and physiological components of variations in tree-ring cellulose δ18 O and δ2 H in order to remove the age trend. This enabled us to evaluate the climatic record from cellulose δ18 O variations. The extracted climatological component in the cellulose δ18 O for the past 2600 years in central Japan was well correlated with numerous instrumental, historical, and paleoclimatological records of past summer climate at various spatial and temporal scales. This indicates that integration of tree-ring cellulose δ18 O and δ2 H data is a promising method to reconstruct past summer climate variations on annual to millennial timescales, irrespective of the growth environment. However, analytical and statistical methods need to be improved for further development of this climate proxy. [ABSTRACT FROM AUTHOR]

Background: In Japan, hepatitis C virus (HCV)-infected patients with decompensated cirrhosis currently have no treatment options. In this Phase 3 study, we evaluated sofosbuvir-velpatasvir with or without ribavirin for 12 weeks in patients with any HCV genotype and decompensated cirrhosis [Child-Pugh-Turcotte (CPT) class B or C] in Japan.Methods: Patients were randomized 1:1 to receive sofosbuvir-velpatasvir with or without ribavirin for 12 weeks. Randomization was stratified by CPT class and genotype. Sustained virologic response 12 weeks following completion of treatment (SVR12) was the primary efficacy endpoint.Results: Of the 102 patients enrolled, 57% were treatment naive, 78% and 20% had genotype 1 and 2 HCV infection, respectively, and 77% and 20% had CPT class B and C cirrhosis, respectively, at baseline. Overall, 61% of patients were female and the mean age was 66 years (range 41-83). SVR12 rates were 92% (47/51) in each group. Among patients who achieved SVR12, 26% had improved CPT class from baseline to posttreatment week 12. Most adverse events (AEs) were consistent with clinical sequelae of advanced liver disease or known toxicities of ribavirin. Four patients (8%) who received sofosbuvir-velpatasvir and seven (14%) who received sofosbuvir-velpatasvir plus ribavirin experienced a serious AE. The 3 deaths (bacterial sepsis, gastric varices hemorrhage, hepatocellular carcinoma) were attributed to liver disease progression.Conclusion: Sofosbuvir-velpatasvir for 12 weeks provides a highly effective and well-tolerated therapy for Japanese patients with HCV and decompensated cirrhosis. Ribavirin did not improve efficacy but increased toxicity. [ABSTRACT FROM AUTHOR]

Haruna volcano, located in central Japan, erupted the Hr-FA and Hr-FP tephras during a period of several decades around the 6th century. To estimate the precise age of the second eruption, we performed AMS radiocarbon dating on a charred wood trunk (29 rings) collected from a pyroclastic flow deposit of the Hr-FP, and obtained a year range of cal AD 424–444 (2σ) using 14C wiggle matching of seven dates with the IntCal13 dataset. However, this result is approximately 100 years older than the inferred calendar year from Sue pottery and Kofun (ancient tomb mound) chronologies and is also inconsistent with the stratigraphic relation of the Hr-FA and Hr-FP. For the 5−6th centuries when the Hr-FP might have erupted, 14C dating was performed on Japanese trees whose precise chronologies were established dendrochronologically. The 14C ages of the annual rings of these trees showed local offsets about 30 years older than those of IntCal13. This tendency has been observed in several studies on trees in Japan and is consistent with the results from the Japanese cedar tree. As a preliminary study, the Hr-FP data were wiggle matched with the existing local dataset for AD 340–545 obtained from one tree in central Japan. The year of the outermost annual ring of the sample tree collected in the Hr-FP tephra is estimated to be cal AD 538−559 (79.0% probability). This estimated age of the Hr-FP eruption is consistent with the archaeological chronology (Sue pottery and Kofun) and tephrochronology around Haruna volcano. [ABSTRACT FROM AUTHOR]

Little is known about the spatiotemporal dynamics of gray wolves in the Pleistocene across low-latitude regions of Eurasia. In Japan, a small-bodied endemic subspecies of Japanese wolves existed and went extinct in the early 1900s. The fossil record indicates that a giant wolf, which reached 70 cm in body height, inhabited Japan during the Pleistocene, but its evolutionary relationship, if any, with the Japanese wolf remains uncertain. Here, to reveal the genetic origin of the Japanese wolf, we analyzed ancient DNA from remains (recovered in Japan) of one Pleistocene wolf that lived 35,000 years ago and one Holocene wolf from 5,000 years ago. The analysis of the mitochondrial DNA revealed that the Pleistocene wolf was not part of the Japanese wolf clade but rather an earlier-diverging lineage. The analysis of the nuclear DNA of the Holocene Japanese wolf revealed that it was an admixture of the Japanese Pleistocene wolf and continental wolf lineages. These findings suggest that the Japanese wolf originated via waves of colonization of multiple Pleistocene wolf populations at 57–35 and 37–14 ka, respectively, followed by interpopulation hybridization. [Display omitted] • Ancient DNA of 35,000- and 5,000-year-old wolf fossils found in Japan are analyzed • The Pleistocene giant wolf was one of the early-diverging Pleistocene wolf lineages • An admixed genome of the Japanese wolf suggests its unique origin via hybridization • Repeated wolf expansions caused a complex colonization history in Japanese islands Segawa et al. report ancient DNA from fossils of a giant Pleistocene wolf that lived 35,000 years ago and a Japanese wolf (Canis lupus hodophilax) that lived 5,000 years ago. This small-bodied extinct subspecies was an admixture of the Pleistocene wolf in Japan and continental wolf lineages. Repeated migration of ancient wolves resulted in a complex colonization history. [ABSTRACT FROM AUTHOR]

Abstract: Wood is present in many cultural heritage objects in Japan thanks to its capacity to resist over a long period of time. However, the evolution of its properties in regular use remains insufficiently known. The present study on the effect of wood aging takes advantage of the Japanese context where building traditions have been maintained for centuries. 3-point bending tests were performed in longitudinal (L) and radial (R) directions on small clear wood specimens cut from 8 historical samples and one modern reference considered of high quality by craftsmen. Although aged wood appeared more rigid and stronger than recent wood, after density and humidity corrections were applied no significant variation of L and R rigidity or L strength was observed. The post-linear behaviour, however, was drastically influenced by wood age especially in R direction where the strength and rupture energy decreased markedly with the time elapsed since the wood was processed. Well preserved aged wood considered as safe as long as it is not loaded perpendicular to grain. To cite this article: M. Yokoyama et al., C. R. Physique 10 (2009). [Copyright &y& Elsevier]

Aim: To study how lymph node metastasis (LNM) risk is stratified in undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations of risk factors., Methods: Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using clinicopathological factors of patient age, location, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by conventional statistical analysis and data-mining analysis., Results: LNM was positive in 44 of 567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis. In preoperatively evaluable factors excluding LVI, sm and > 2 cm were independent factors. According to the depth and size, cases were categorized into the low-risk group [m and ≤ 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%; and sm and ≤ 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than 28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases even in the moderate- and high-risk groups., Conclusion: LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively. Among these factors, LI was the most significantly correlated factor.

Unlabelled: To comprehensively characterize the contribution of virological factors as well as interleukin-28B (IL28B) single-nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated-interferon plus ribavirin (Peg-IFN/RBV) therapy for chronic hepatitis C virus (HCV)-1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino-acid (aa) sequence study in 103 consecutive HCV-1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding-window comparison analysis to characterize response-specific viral sequences, along with IL28B SNP analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), nonearly viral response (nEVR), sustained virological response (SVR), or relapse, the following regions were extracted as most significantly associated with the different responses respectively: nonstructural protein 5A (NS5A) aa.2224-2248 (P = 1.2E-07); core aa.70 (P = 4E-04); NS5A aa.2340-2382 (P = 7.0E-08); and NS5A aa.2360-2377 (P = 1.1E-05). Those NS5A regions nearly coincided with the interferon (IFN) sensitivity-determining region (NS5A aa.2209-2248) and the IFN/RBV resistance-determining region (NS5A aa.2339-2379). In a multivariate analysis, the IL28B SNP (odds ratio [OR] = 16.8; P = 0.009) and NS5A aa.2340-2382 (OR = 13.8; P = 0.0003) were extracted as the two most-significant independent variables contributing to the final outcome., Conclusion: In Peg-IFN/RBV therapy, polymorphisms in IL28B, NS5A aa.2224-2248, core aa.70, and, most important, NS5A aa.2340-2382 have a tremendous influence on treatment response in association with viral kinetics, resulting in significantly different outcomes in chronic HCV-1b infection., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background & Aims: Pegylated interferon and ribavirin (PEG-IFN/RBV) therapy for chronic hepatitis C virus (HCV) genotype 1 infection is effective in 50% of patients. Recent studies revealed an association between the IL28B genotype and treatment response. We aimed to develop a model for the pre-treatment prediction of response using host and viral factors., Methods: Data were collected from 496 patients with HCV genotype 1 treated with PEG-IFN/RBV at five hospitals and universities in Japan. IL28B genotype and mutations in the core and IFN sensitivity determining region (ISDR) of HCV were analyzed to predict response to therapy. The decision model was generated by data mining analysis., Results: The IL28B polymorphism correlated with early virological response and predicted null virological response (NVR) (odds ratio=20.83, p<0.0001) and sustained virological response (SVR) (odds ratio=7.41, p<0.0001) independent of other covariates. Mutations in the ISDR predicted relapse and SVR independent of IL28B. The decision model revealed that patients with the minor IL28B allele and low platelet counts had the highest NVR (84%) and lowest SVR (7%), whereas those with the major IL28B allele and mutations in the ISDR or high platelet counts had the lowest NVR (0-17%) and highest SVR (61-90%). The model had high reproducibility and predicted SVR with 78% specificity and 70% sensitivity., Conclusions: The IL28B polymorphism and mutations in the ISDR of HCV were significant pre-treatment predictors of response to PEG-IFN/RBV. The decision model, including these host and viral factors may support selection of optimum treatment strategy for individual patients., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

AMS (Accelerator Mass Spectrometry) radiocarbon dates for eight potsherds from a single piece of pottery from a wetland archaeological site indicated that charred material from the inner pottery surfaces (5052 ± 12 BP; N = 5) is about 90 (14)C years older than that from the outer surfaces (4961 ± 22 BP; N = 7). We considered three possible causes of this difference: the old wood effect, reservoir effects, and diagenesis. We concluded that differences in the radiocarbon ages between materials from the inner and outer surfaces of the same pot were caused either by the freshwater reservoir effect or by diagenesis. Moreover, we found that the radiocarbon ages of carbonized material on outer surfaces (soot) of pottery from other wetland archaeological sites were the same as the ages of material on inner surfaces (charred food) of the same pot within error, suggesting absence of freshwater reservoir effect or diagenesis.