Uptake of P(i) at the cellular membrane is essential for the maintenance of cell viability. However, phosphate overload is also stressful for cells and can result in cellular damage. In the present study, we investigated the effects of the transgenic overexpression of type III P(i) transporter Pit-1 to explore the role of extracellular P(i) in glomerular sclerosis during chronic renal disease. Pit-1 transgenic (TG) rats showed progressive proteinuria associated with hypoalbuminemia and dyslipidemia. Ultrastructural analysis of TG rat kidney by transmission electron microscopy showed a diffuse effacement of the foot processes of podocytes and a thickening of the glomerular basement membrane, which were progressively exhibited since 8 wk after birth. TG rats died at 32 wk of age due to cachexia. At this time, more thickening of the glomerular basement membrane and segmental sclerosis were observed in glomeruli of the TG rats. Immunohistochemical examination using anti-connexin 43 and anti-desmin antibodies suggested the progressive injury of podocytes in TG rats. TG rats showed higher P(i) uptake in podocytes than wild-type rats, especially under low P(i) concentration. When 8-wk-old wild-type and TG rats were fed a 0.6% normal phosphate (NP) or 1.2% phosphate (HP) diet for 12 wk, HP diet-treated TG rats showed more progressive proteinuria and higher serum creatinine levels than NP diet-treated TG rats. In conclusion, our findings suggest that overexpression of Pit-1 in rats induces phosphate-dependent podocyte injury and damage to the glomerular barrier, which result in the progression of glomerular sclerosis in the kidney.

Apart from certain studies on Macrocystis pyrifera (Linnaeus) C. Agardh, very few in situ experimental studies on production have been carried out to verify that "bottom-up effects" (relating to nutrient supply) are more important than "top-down" effects (relating to herbivory) in temperate kelp forests. The effects of nutrient supply on recruitment and production of hatchery-raised gametophytes of Saccharina japonica, cultivated on a rope, and wild Saccharina religiosa, cultivated on a rope and on new concrete reefs placed at the sea bottom, were examined at an experimental site with artificial nutrient addition continuously from without nutrient supply, at a natural site in Tomari (Sea of Japan, southwestern Hokkaido, Japan). At both sites, sea urchins were removed for exclusion of top-down effect. At the natural site, no hatchery-raised S. japonica and wild S. religiosa grew on the rope. No wild S. religiosa grew on the porous-concrete reefs and rocks. At the nutrient-enhanced site, S. japonica and S. religiosa grew rapidly on the rope, at rates of 47.7 and 33.3 plants/10 cm length rope, respectively. S. religiosa grew on the concrete reefs at a concentration of 9.7 plants/0.3 m 2 . At the nutrientenhanced site, the concentrations of NH 4 -N, NO 3 -N, NO 2 -N, and PO 4 -P ranged from 35.2-173.2, 2.1-10.9, 0.3-1.5, and 0.8-2.6 μmol L −1 , respectively, being markedly higher than those at the natural site, where these nutrient concentrations were almost equal to the averages off Tomari. These results indicate that the production of Saccharina kelp is restricted by bottom-up effects (at a low nutrient concentration) in the Sea of Japan, southwestern Hokkaido. Nutrient supply would be essential for growth enhancement of Saccharina kelp production in a marine environment around Japan where, in recent times, water temperatures have increased by ca. 0.5°C and nutrient concentrations have decreased.

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The ability to handle evolving graph structures is important both for programming languages and modeling languages. Of various languages that adopt graphs as primary data structures, a graph rewriting language LMNtal provides features of both (concurrent) programming languages and modeling languages, and its implementation unifies ordinary program execution and model checking functionalities. Unlike pointer manipulation in imperative languages, LMNtal allows us to manipulate graph structures in such a way that the well-formedness of graphs is guaranteed by the language itself. However, since the shapes of graphs can be complex and diverse compared to algebraic data structures such as lists and trees, it is a non-obvious important task to formulate types of graphs to verify individual programs. With this motivation, this paper discusses LMNtal ShapeType, a type checking framework that applies the basic idea of Structured Gamma to a concrete graph rewriting language. Types are defined by generative grammars written as LMNtal rules, and type checking of LMNtal programs can accordingly be done by exploiting the model checking features of LMNtal itself. We gave a full implementation of type checking exploiting the features of the LMNtal meta-interpreter and confirmed that it works for practical operations on various graph structures, including single-step and multi-step operations on non-algebraic data structures and data structures with numerical shape constraints.

Graphs are a generalized concept that encompasses more complex data structures than trees, such as difference lists, doubly-linked lists, skip lists, and leaf-linked trees. Normally, these structures are handled with destructive assignments to heaps, which is opposed to a purely functional programming style and makes verification difficult. We propose a new purely functional language, λ GT , that handles graphs as immutable, first-class data structures with a pattern matching mechanism based on Graph Transformation and developed a new type system, F GT , for the language. Our approach is in contrast with the analysis of pointer manipulation programs using separation logic, shape analysis, etc. in that (i) we do not consider destructive operations but pattern matchings over graphs provided by the new higher-level language that abstract pointers and heaps away and that (ii) we pursue what properties can be established automatically using a rather simple typing framework.