Hydrological environment affects the nutrient retention and runoff function of naturally re-wetted agricultural peatland in lowland river floodplain.

Re-wetting of agricultural areas reclaimed by draining peatlands reportedly entails risks of nutrient loads downstream because of leaching of dissolved nutrients from pools in the soil. On floodplain fens, nutrient retention and runoff function have been recognized as dependent upon the hydrological environments of re-wetted agricultural peatland (RAP). Although many studies have been conducted for artificially re-wetted agricultural peatlands (artificial RAPs), knowledge on naturally re-wetted agricultural peatlands (natural RAPs) has been lacking. This study assessed the natural re-wetting of agricultural areas in floodplain fens in terms of risks of nutrient loading in the basin of Kushiro Mire, northern Japan. Flooding of the adjacent river caused by heavy rainfall remarkably increased the water flow, and the inflow and outflow fluxes of nitrogen (N) and phosphorus (P) of a test plot in the natural RAP. Flood waters supplied mainly inorganic nutrients to the test plot, including NO3-N and PO4-P. Larger amounts of dissolved organic N and P, NH4-N, and PO4-P that had accumulated in surface water and surface groundwater in the plot flowed out. Consequently, the test plot represented net runoff of 3 and 0.4 mg m-2 day-1 as total N and total P, respectively, for the average of the whole observation period. The test plot was a source of N loading downstream, which was contrary to results obtained for artificial RAPs in many studies. However, the test plot showed a smaller amount of net phosphorus runoff. Our findings suggest that water level fluctuation and river flood water inflow affect the nutrient retention and runoff functions of RAPs. Repeated inundated and dried conditions, with no continuous inflow of river water, explain the nutrient runoff in the test plot.

Metapopulation stability in branching river networks.

Intraspecific population diversity (specifically, spatial asynchrony of population dynamics) is an essential component of metapopulation stability and persistence in nature. In 2D systems, theory predicts that metapopulation stability should increase with ecosystem size (or habitat network size): Larger ecosystems will harbor more diverse subpopulations with more stable aggregate dynamics. However, current theories developed in simplified landscapes may be inadequate to predict emergent properties of branching ecosystems, an overlooked but widespread habitat geometry. Here, we combine theory and analyses of a unique long-term dataset to show that a scale-invariant characteristic of fractal river networks, branching complexity (measured as branching probability), stabilizes watershed metapopulations. In riverine systems, each branch (i.e., tributary) exhibits distinctive ecological dynamics, and confluences serve as "merging" points of those branches. Hence, increased levels of branching complexity should confer a greater likelihood of integrating asynchronous dynamics over the landscape. We theoretically revealed that the stabilizing effect of branching complexity is a consequence of purely probabilistic processes in natural conditions, where within-branch synchrony exceeds among-branch synchrony. Contrary to current theories developed in 2D systems, metapopulation size (a variable closely related to ecosystem size) had vague effects on metapopulation stability. These theoretical predictions were supported by 18-y observations of fish populations across 31 watersheds: Our cross-watershed comparisons revealed consistent stabilizing effects of branching complexity on metapopulations of very different riverine fishes. A strong association between branching complexity and metapopulation stability is likely to be a pervasive feature of branching networks that strongly affects species persistence during rapid environmental changes.

Effect of leucovorin on the antitumor efficacy of the 5-FU prodrug, tegafur-uracil, in human colorectal cancer xenografts with various expression levels of thymidylate synthase.

The combination of oral tegafur-uracil (UFT) with leucovorin (LV) is used to treat patients with stage II to III colon cancer based on the results of postoperative randomized studies in which UFT/LV treatment showed an equivalent efficacy to intravenous 5-FU plus LV therapy. However, whether the addition of LV to UFT can elevate the antitumor activity of UFT in colorectal tumors with high expression levels of thymidylate synthase (TS), which affects 5-FU efficacy, remains to be clarified. This study investigated the effect of LV on the antitumor activity of UFT and/or 5-FU prodrugs in low folate diet-fed nude mice using human colorectal cancer xenografts with various expression levels of TS. The addition of LV to UFT resulted in a 55-79% inhibition of tumor growth among 11 types of colorectal tumor xenograft, whereas UFT alone showed 23-67% antitumor activity. Although there was an inverse relationship between the antitumor effect of UFT alone and UFT plus LV and tumoral TS activity, UFT plus LV appeared to have a more potent antitumor effect than UFT alone on colorectal tumors such as Co-3 and KM12C/5-FU with high expression levels of TS. This finding was confirmed by the significant positive correlation between the relative inhibition ratio of UFT/LV to UFT alone and TS levels in tumors. To investigate the reason for the higher efficacy of UFT/LV on colorectal cancer xenografts with high TS activity, intratumoral levels of reduced folates and a ternary complex of TS after oral UFT with or without LV were measured using Co-3 xenografts. Elevated levels of reduced folates and an increased ternary complex of TS in LV-treated tumors were noted. Our results indicate that a combined therapy of UFT with LV may contribute to the treatment of colorectal cancer patients with low and high expression levels of tumoral TS by increased formation of the ternary complex of TS leading to potentiated antitumor efficacy of UFT.

Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation.

The maturation of dendritic cells (DCs) after exposure to microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady-state conditions, triggered by alterations in E-cadherin-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the beta-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These DCs induced tolerance in vivo and may thus contribute to the elusive steady-state "tolerogenic DCs."

Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome.

A 14-year-old Japanese girl with a progressing combined immunodeficiency had developed non-Hodgkin's diffuse large B cell lymphoma. Her molecular analysis showed a compound heterozygote of novel mutations in the LIG4 gene, M249V substitution and a five nucleotides deletion from nucleotide position 1,270-1,274. She had also a set of characteristic clinical features of LIG4 syndrome. Mutations in the LIG4 gene, which plays a critical role in the repair of DNA double-strand breaks, imply a correlation with malignancies and several cases with leukemia or lymphoma have already been reported. We report here on a case of LIG4 syndrome complicated with distinct EBV-associated B-cell lymphoma.

Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1, by distinct human dendritic cell populations.

Dendritic cells (DCs) play a critical role in initiating antigen-specific immune responses, because they are able to capture exogenous antigens for presentation to naive T cells on both MHC class I and II molecules. As such, DCs represent important elements in the development of vaccine therapy for cancer. Although DCs are known to present antigens from phagocytosed tumor cells or preprocessed peptides, we explored whether they might also present soluble recombinant NY-ESO-1, a well characterized cancer antigen. We compared the abilities of human monocyte-derived DCs and DCs derived in vitro from CD34-positive stem cells to present NY-ESO-1 epitopes to MHC class I-restricted cytotoxic T cells. Although monocyte-derived DCs did not efficiently crosspresent free NY-ESO-1 protein, IgG-immune complexes containing NY-ESO-1 were avidly presented after uptake by Fcgamma receptors (FcgammaRII). In contrast, CD34-derived DCs were unable to process either soluble or immune complexed NY-ESO-1, although they efficiently presented preprocessed NY-ESO-1 peptides. This difference did not necessarily correlate with endocytic capacity. Although monocyte-derived DCs exhibited greater fluid-phase uptake than CD34-derived DCs, the two populations did not differ with respect to their surprisingly limited capacity for Fcgamma receptor-mediated endocytosis. These results indicate that monocyte-derived DCs will be easier to load by using protein antigen in vitro than CD34-derived DCs, and that the latter population exhibits a restricted ability to crosspresent soluble exogenous antigens.