Isolation of Araguspongine M,a New Stereoisomer of an Araguspongine/Xestospongin alkaloid,and Dopamine from the Marine Sponge Neopetrosia exigua Collected in Palau

A new stereoisomer of an araguspongine/xestospongin alkaloid, named araguspongine M (1), has been isolated together with 12 known compounds, araguspongines B (2) and D (3), dopamine, three galactosyl diacylglycerols, 24-methyl cholesterol, 5,6-dihydrocholesterol, β-sitosterol, and three 5α,8α-epidioxy sterols (11–13), from the marine sponge Neopetrosia exigua (formerly Xestospongia exigua) collected in Palau. The structure of 1 was assigned on the basis of its spectral data analysis. This is the first report on the isolation of dopamine from a marine sponge. This compound may be produced by an endosymbiotic Synechococcus-like cyanobacterium. Compounds 1–3 and 11–13 showed cytotoxicity against HL-60 at IC₅₀’s of 5.5, 5.5, 5.9, 22.4, 9.5, and 9.6 μM, respectively. The possible biosynthesis origin of the isolated metabolites is discussed.     

Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma

Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately evaluate their efficacy, as well as the lack of an adequate technical protocol for efficient transplantation and engraftment of sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in this study, we sought to identify the optimal type of sarcoma and develop a protocol for generating a PDX model. We characterized a PDX mouse model using histopathological and immunohistochemical analyses to determine whether it would show pathological characteristics similar to those of human sarcomas. We achieved engraftment of one of the 10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massive proliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor of pleomorphic leiomyosarcoma and maintained their histological structure in all passages. Moreover, immunohistochemical analysis revealed the expression of specific markers of differentiation to smooth muscle, which is consistent with the features of leiomyosarcoma. We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at least one aspect of human sarcomas, and we believe that this model will facilitate the development of novel therapies for sarcomas.     

Evaluation of the Affinity of Some Toxic Elements to Schwertmannite in Natural Streams Contaminated with Acid Mine Drainage

In order to evaluate fixation potential of schwertmannite for fluvial transport of various toxic elements, we examined bottom precipitates and stream waters collected from the rivers contaminated with acid mine drainage (AMD), which arose from the abandoned Nishinomaki mine (Shimonita, Gunma, Japan). Mineralogical and morphological observations revealed that schwertmannite was the main mineral of the precipitates. The affinity of various toxic ions to schwertmannite was evaluated on the basis of (1) apparent solid?Cliquid partition coefficients (K _d??s) between precipitates and stream waters, (2) coprecipitation behaviors during schwertmannite formation in a laboratory test, and (3) consideration on coprecipitation processes using partial charge model (PCM). As a result, oxyanions of V, As, Mo and Sb, K _d??s of which were relatively large (>10⁴ (ml g^?1)), were considered to be immobilized by schwertmannite precipitates. A laboratory test also demonstrated that these ions except Mo coprecipitated with schwertmannite. In addition, partial charges and average electronegativities predicted on the basis of PCM suggested that the oxyanions of V, As, Mo, and Sb could create stable inner sphere complexes with schwertmannite embryos, which results in their high affinity to schwertmannite. On the other hand, cationic ions of Mn, Cu, Zn, Sr, Cs, and U, K _d??s of which were relatively small (<10⁴ (ml g^?1)), were thought to have a tendency to flow downstream without uptake by schwertmannite precipitates. All these results suggested that schwertmannite has high fixation potential for fluvial transport of various toxic oxyanions in AMD-contaminated rivers.     

Verrucarin A Inhibition of MAP Kinase Activation in a PMA-stimulated Promyelocytic Leukemia Cell Line

Verrucarin A is an inhibitor of protein synthesis. In this study, we examined the inhibitory action of verrucarin A on signal molecules. Verrucarin A partially inhibited the IL-8 production of a PMA-stimulated promyelocytic leukemia cell line (HL-60 cells), and the effect was related to the inhibition of NF-κB activation at non-cytotoxic concentrations. Moreover, the inhibition of mitogen activated protein (MAP) kinase by verrucarin A was especially strong with p38- and JNK-phosphorylation. The findings show a new action of verrucarin A, and it is expected that this action relaxes the signal activation in response to stress.     

Root temperature drives winter acclimation of shoot water relations in Cryptomeria japonica seedlings

In many temperate evergreen plant species, reductions in turgor loss point of leaves (Psi(tlp)) and leaf osmotic potential at full turgor (pi(sat)) occur from late summer to winter. To test the hypothesis that this seasonal change in leaf water relations is driven by root temperature, we manipulated the temperature of the roots and shoots of Cryptomeria japonica D. Don seedlings separately. Whole-plant warming diminished the seasonal changes in shoot water relations observed in the control plants, whereas shoot warming did not. Compared with the controls, root warming diminished the change in Psi(tlp) but not in pi(sat), whereas cooling accelerated the seasonal changes in shoot water relations. These results indicate that: (1) temperature responses of roots are involved in the seasonal changes in Psi(tlp) from late summer to winter; and (2) root temperature is partly responsible for the simultaneous changes in pi(sat). Whole-plant cooling caused increased root hydraulic resistance, suggesting that seasonal changes in shoot water relations represent adaptive responses to increased root hydraulic resistance at low root temperatures.     

Screening for condensed tannin-degrading fungi with a synthetic <Superscript>14</Superscript>C-labeled compound

To find fungi that are potent for degradation of condensed tannin, a two-step screening was used. This involved measurement of fungal growth rate on Japanese cedar (Cryptomeria japonica) bark, followed by determination of [¹⁴C]-labeled CO₂ generated from fungal degradation of synthetic [¹⁴C]-labeled condensed tannin model. In the first screening, 75 strains of wood rot fungi were tested, and 19 strains effectively decreased bark weight and/or the weight of the methanol-soluble fraction. For the second screening, [¹⁴C]-labeled condensed tannin model compound was synthesized in 11.8% yield based on radioactivity measurements. Over the incubation period, Coriolus hirsutus K-2671, Lentinus edodes Is, and Lampteromyces japonicus Nn showed higher cumulative [¹⁴C]-labeled CO₂ emissions than the other strains and mineralized the [¹⁴C]-labeled condensed tannin model compound by 3.7%, 3.0%, and 3.0%, respectively. Fractionation of the methanol extracts from the medium by gel permeation chromatography after fungal treatment suggested that fungi that can induce the emission of significant levels of [¹⁴C]-labeled CO₂ can extensively depolymerize condensed tannins.     

Background data of 2-year-old male and female F344 gpt delta rats

Although gpt delta rats, as reporter gene-transgenic rats, were originally developed for in vivo mutation assays, they have also been used to evaluate chemical carcinogenesis and comprehensive toxicity. Therefore, it is necessary to accumulate background data on carcinogenicity and general toxicity in gpt delta rats. Here, we investigated the background data of 110-week-old male and female F344 gpt delta rats and wild-type rats. There was no effect of reporter gene transfection on animal survival rates and body weights during the experiment. The relative weight of male gpt delta rat adrenals was significantly higher than that of wild-type rats, possibly due to the higher incidence of pheochromocytoma. There were no intergenotype differences in the incidence of nonneoplastic lesions in both sexes, including chronic progressive nephropathy and focus of cellular alteration in the liver, which had a higher incidence in both genotypes. Additionally, the significantly higher incidence of adrenal pheochromocytoma in male gpt delta rats than that in wild-type rats was likely incidental because of the lack of differences in the incidences of preneoplastic (male and female) and neoplastic (female) adrenal lesions in both genotypes. Other neoplastic lesions in both sexes showed no intergenotype differences in incidence rates, although large granular lymphocytic leukemia in the spleen and Leydig cell tumors in the testes of males showed higher incidence rates. Overall, there were no effects of reporter gene transfection on the spectrum of spontaneous lesions in F344 gpt delta rats, thus supporting their applicability in evaluating chemical toxicity and carcinogenicity.     

Ectomycorrhizal Association Enhances Al Tolerance by Inducing Citrate Secretion in Pinus densiflora

To investigate the effects of ectomycorrhizal association on the aluminum (Al) tolerance of Pinus densiflora Sieb. & Zucc., seedlings with or without ectomycorrhizal association with the fungus Pisolithus tinctorius (Pers.) Coker & Couch were exposed to 1 mM Al. Association with P. tinctorius alleviated Al-induced inhibition of root elongation and biomass growth in the mycorrhizal seedlings. Secretion of malate and citrate, both low-molecular-weight organic acids that could detoxify Al by the formation of stable complexes, was investigated in P. tinctorius mycelia and in pine roots with and without P. tinctorius association. Citrate secretion from the P. tinctorius mycelia in vitro was stimulated by Al. Citrate secretion from the roots of the ectomycorrhizal seedlings was also stimulated by Al, but was not detected in the non-mycorrhizal seedlings. These results suggest that citrate secreted from the roots of the ectomycorrhizal seedlings was produced in the hyphae of P. tinctorius. Citrate secretion may play a role in enhancing the Al tolerance of host seedlings.     

Remnants of the early solar system water enriched in heavy oxygen isotopes

Oxygen isotopic composition of our solar system is believed to have resulted from mixing of two isotopically distinct nebular reservoirs, 16O-rich and (17,18)O-rich relative to Earth. The nature and composition of the (17,18)O-rich reservoir are poorly constrained. We report an in situ discovery of a chemically and isotopically unique material distributed ubiquitously in fine-grained matrix of a primitive carbonaceous chondrite Acfer 094. This material formed by oxidation of Fe,Ni-metal and sulfides by water either in the solar nebula or on a planetesimal. Oxygen isotopic composition of this material indicates that the water was highly enriched in 17O and 18O (delta(17,18)O(SMOW) = +180 per thousand per mil), providing the first evidence for an extremely (17,18)O-rich reservoir in the early solar system.