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Study region: A legacy underground tungsten mine in a mountainous area, central Japan. Study focus: We analyzed mining-influenced water (MIW) from mine voids and surface water from rivers to determine the dissolved ion concentrations and water isotopes (δ18O and δ2H). The results were interpreted using principal components and cluster analyses, as well as Eh-pH (Pourbaix) diagram. By integrating the obtained analytical results with mine-related data, we conducted component separation of MIW and estimation of their origins. New hydrological insights for the region: The MIW and part of surface water were characterized by the SO42− and F− generated via the dissolution of sulfide minerals and fluorite (CaF2) from the ore deposit. MIW components were successfully separated using these indicators and water isotopes. The results of component separation indicated that the MIW consisted of two components, namely infiltrating water that rapidly passes through upper mine voids to reach the mine void at ground level, and groundwater that undergoes some degree of residence time before flowing into the ground level void from shaft I.

Summary: Non-canonical Wnt signaling activated by Wnt5a/Wnt11 is required for the second heart field development in mice. However, the pathophysiological role of non-canonical Wnt signaling in the adult heart has not been fully elucidated. Here we show that cardiomyocyte-specific Wnt5a knockout mice exhibit improved systolic function and reduced expression of mechanosensitive genes including Nppb when subjected to pressure overload. In cultured cardiomyocytes, Wnt5a knockdown reduced Nppb upregulation induced by cyclic cell stretch. Upstream analysis revealed that TEAD1, a transcription factor that acts with Hippo pathway co-activator YAP, was downregulated both in vitro and in vivo by Wnt5a knockdown/knockout. YAP nuclear translocation was induced by cell stretch and attenuated by Wnt5a knockdown. Wnt5a knockdown-induced Nppb downregulation during cell stretch was rescued by Hippo inhibition, and the rescue effect was canceled by knockdown of YAP. These results collectively suggest that Wnt5a-YAP signaling axis mediates mechanotransduction in cardiomyocytes and contributes to heart failure progression.

Abstract This paper described the use of fly ash for soil amelioration of acidic soils to promote plant growth. In mining sites, acid sulfate soils/rocks, which contain sulfide minerals (e.g. pyrite FeS2), have appeared as a result of overburden excavation. The excessively acidic condition inhibits plant growth due to the dissolution of harmful elements, such as Al, Fe, and Mn. Fly ash, an alkaline byproduct of coal combustion generated in thermal power plants is expected to be adopted to ameliorate acidic soils. However, the mixing ratio of fly ash must be considered because excessive addition of fly ash can have a negative impact on plant growth due to its physical/chemical properties. The pot trials using Acacia mangium demonstrate the evolution of plant growth with a 5%–10% addition of fly ash into acidic soil. When the acidic soil has a high potential for metal dissolution, the metal ions leached from the acidic soil are large, making it difficult to improve plant growth due to osmotic and ionic stress. This work suggests that the effects of fly ash on metal ions leached from the soil have to be considered for the amelioration of acidic soil.

For a total of 80 legacy mines in Japan, by assuming that untreated mine drainages were discharged and that metal loadings from sources other than mine drainage were negligibly small, we estimated seven element concentrations (Cd, Pb, As, Cu, Zn, Fe, and Mn) at water quality monitoring (WQM) river sites closest to individual mines (hereinafter referred to as the closest WQM sites) based on a simple dilution approach. In addition, for zinc as an example, the concentrations at the closest WQM sites were estimated by taking account into estimated zinc loadings from sources other than mine drainage. Results of the former analysis showed that the concentrations of all four elements (Cd, Pb, As, and Zn) at the closest WQM sites were predicted to be below Japanese environmental water quality standards in 50% of the legacy mines analyzed, which is not a small percentage. However, the result of the latter analysis showed that the contributions of treated mine drainages to the total loadings of zinc at the closest WQM sites were less than 50% in approximately 88% of the legacy mines analyzed. This result suggests that metal loadings from sources other than mine drainages at the closest WQM sites are not trivial in many legacy mines. Even if untreated mine drainages were discharged, estimated zinc concentrations in 72% of the WQM sites, where the annual average of measured concentrations of total zinc was below the environmental water quality standard (0.03 mg/L), were still below the standard. Despite a screening-level assessment based on multiple assumptions such as the simple dilution, results of the present study should be valuable for understanding the impact of discharging untreated mine drainages on metal concentrations in rivers receiving those from the legacy mines toward applying the water-quality management that secures the protection of downstream water use.

Abstract Background Human T‐lymphotropic virus‐1 (HTLV‐1)+ Hodgkin lymphoma (HL) is difficult to differentiate from adult T‐cell leukemia/lymphoma (ATLL) with HL‐like histology (HL‐like ATLL). Methods Cytological and immunohistological features, HTLV‐1 proviral DNA integration, and rearrangements of the T‐cell receptor (TCR) Cβ1 gene were examined in 11 HTLV‐1+ patients with HL‐like disease. Results Six patients were classified as HTLV‐1+ HL and five as HL‐like ATLL in accordance with genetic findings of HTLV‐1 proviral DNA integration and rearrangements of the TCR Cβ1 gene. Small ordinary looking lymphocytes with round nuclei were detected in the background of six patients with HTLV‐1+ HL, which were immunohistochemically negative for CD25 and CC chemokine receptor (CCR)4 and had a low MIB1 labeling index (mean: 28.3%). In the HL‐like ATLL specimens, small‐ and medium‐sized atypical lymphocytes with indented and irregular‐shaped nuclei were found, and were diffusely positive for CD25 and CCR4, with high MIB1 labeling (mean: 76%). Both groups had scattered CD30+ and CD15+ Hodgkin and Reed Sternberg (RS) giant cells, with or without CD20 expression and Epstein‐Barr virus infection. The 50% overall survival period was significantly longer for the HTLV‐1+ HL group (180 months) than for the HL‐like ATLL group (7.8 months; P = .004). Conclusions HTLV‐1+ HL showed typical small lymphoid cells with a low MIB1 labeling index in a background of Hodgkin and RS cells, with some scattered CD25+ and CCR4+ lymphocytes. In HTLV‐1 endemic areas, distinguishing HTLV‐1+ HL from HL‐like ATLL is important because of their differing treatment strategies and prognoses.

Pancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF–RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in pancreatic cancer patients and showed that its localization to invasive pseudopods is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to invasive pseudopods. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide against ARL4C into tumor-bearing mice suppressed metastasis of pancreatic cancer. These results suggest that ARL4C–IQGAP1–MMP14 signaling is activated at invasive pseudopods of pancreatic cancer cells.

The mechanisms promoting hepatoblastoma (HB) progression through Wnt/β-catenin signaling are unclear. Here, the authors show that the Wnt/ β-catenin axis induces GREB1 expression and nuclear localization, and suppresses TGFβ pathway, and propose GREB1 as a therapeutic target in HB.

Soil erosion is one of the major environmental problems in open-cut mines in tropical regions. It causes negative impacts including the removal of nutrient-rich topsoil, destroys aquatic habitat, dam and pond siltation, clogs river by deposition of sediment, and causes water pollution in the rehabilitation process. Soil texture is an important factor to affect soil erosion. In this study, artificial rainfall experiment in the laboratory scale was conducted to clarify the mechanism of soil erosion under the different soil composition and to discuss the methods for minimizing soil erosion. The obtained results showed that the soil seal generated due to the presence of fine particle under high rainfall intensity is the main contributor to accelerate the soil erosion. Additionally, the surface coverage by the cover crops is the most effective measure to reduce soil erosion because both the coarse and fine contents runoff can be minimized while arranging of the slope angle is effective for reducing the runoff of coarse contents and the soil compaction is effective to reduce that of fine contents. Soil erosion can be minimized by selecting prevention method considering the type of soil because the prevention effect on soil erosion is different depending on the type of soil.

Primary oral diffuse large B cell lymphoma (DLBCL) is rare and the differential diagnosis is difficult due to its low incidence and nonspecific symptoms, which resemble those of common oral diseases in the initial clinical setting. We aimed to discuss the value of making an accurate diagnosis using liquid-based cytology (LBC) and cell block (CB) for not only the morphological interpretation but also cytohistological assessment of oral DLBCL. LBC and CBs made from oral brushing materials were prepared on the first medical examination and a morphological analysis and immunohistochemical analysis of specific biomarkers were performed. The analysis of LBC preparations showed the presence of large-size lymphocytes with large irregular nuclei and prominent nucleoli, suggesting the existence of large B-cell lymphoma. A more detailed histological subclassification of the CB specimen was performed, which was classified as the activated B-cell (ABC) phenotype of DLBCL, by confirming the immunohistochemical expression of CD10−/ B-cell lymphoma 6 (BCL6)+/ multiple myeloma oncogene 1(MUM1)+, which is a significant risk factor in DLBCL. Our findings suggest that the combination of LBC and CB is a useful and informative tool for making an accurate molecular diagnosis of oral DLBCL in cases in which lymphomas are clinically suspected.

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

The increase in the number of coal-fired power plants with the increase in coal production and its consumption has caused the problem of the treatment of a large amount of coal ash in Indonesia. In the past studies, coal ash was applied to postmine land with the aim of improving soil conditions for plant growth; however, heavy rain in the tropical climate may cause soil erosion with the change in soil conditions. This study presents the effects of application of coal ash to postmine land on soil erosion by performing the artificial rainfall test as well as physical testing. The results indicate that the risk of soil erosion can be reduced significantly by applying the coal ash which consists of more than 85% of sand to topsoil in the postmine land at the mixing ratio of over 30%. Additionally, they reveal that not only fine fractions but also microporous structures in coal ash enhance water retention capacity by retaining water in the structure, leading to the prevention of soil erosion. Thus, the risk of soil erosion can be reduced by applying coal ash to topsoil in consideration of soil composition and microporous structure of coal ash.

Characterization of mine waste rocks and prediction of acid mine drainage (AMD) play an important role in preventing AMD. Although high-tech analytical methods have been highlighted for mineral characterization and quantification, simple testing methods are still practical ways to perform in a field laboratory in mines. Thus, this study applied some simple testing methods to the characterization of mine wastes and AMD prediction in addition to a leaching test and the sequential extraction test with HCl, HF, and HNO3, which have not been applied for these purposes, focusing on the form of sulfur and the neutralization effects of carbonates. The results of the Acid Buffering Characteristic Curve test supported the changing trend of the pH attributing carbonates only during the first 10 leaching cycles in the leaching test. The change in the Net Acid Generating (NAG) pH in the sequential NAG test reflected the solubility of sulfur in the rocks, providing information on the form of sulfur in the rocks and the acid-producing potential over time. Consequently, the sequential NAG test and sequential extraction with the acids in combination with the current standards tests (Acid Base Accounting and NAG tests) provided important information for preventing AMD.

Soil water erosion is frequently reported as serious problem in soils in Southeast Asia with tropical climates, and the variations in pH affect the development of the erosion. This study investigated the effects of changes in pH on soil water erosion based on changes in the physical properties of the simulated soils with pH adjusted from 2.0 to 10.0 through artificial rainfall tests. The zeta potential was entirely shifted to positive direction at each pH condition due to Al, Ca, and Mg. In the pH range of 6.0 to 2.0, the aggregation of soil particles resulting from the release of Al3+ from clay minerals and/or molecular attraction between soil particles caused the plastic index (IP) of the soil to decrease. The decrease in IP led to the development of soil water erosion at the pH range. When the pH exceeded 6.0, the repulsive force generated by the negative charges on soil particles decreased IP, resulting in accelerated erosion by water. The results suggest that changes in pH causes physical properties of the soil to change through changes of the zeta potential in the clayey soil rich in Al, Ca, and Mg, leading to the development of soil water erosion.

The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.