Prostaglandin (PG) F 2␣ suppresses adipocyte differentiation by inhibiting the function of peroxisome proliferatoractivated receptor ␥. However, PGF 2␣ synthase (PGFS) in adipocytes remains to be identified. Here, we studied the expression of members of the aldo-keto reductase (AKR) 1B family acting as PGFS during adipogenesis of mouse 3T3-L1 cells. AKR1B3 mRNA was expressed in preadipocytes, and its level increased about 4-fold at day 1 after initiation of adipocyte differentiation, and then quickly decreased the following day to a level lower than that in the preadipocytes. In contrast, the mRNA levels of Akr1b8 and 1b10 were clearly lower than that level of Akr1b3 in preadipocytes and remained unchanged during adipogenesis. The transient increase in Akr1b3 during adipogenesis was also observed by Western blot analysis. The mRNA for the FP receptor, which is selective for PGF 2␣ , was also expressed in preadipocytes. Its level increased about 2-fold within 1 h after the initiation of adipocyte differentiation and was maintained at almost the same level throughout adipocyte differentiation. The small interfering RNA for Akr1b3, but not for Akr1b8 or 1b10, suppressed PGF 2␣ production and enhanced the expression of adipogenic genes such as peroxisome proliferator-activated receptor ␥, fatty acid-binding protein 4 (aP2), and stearoylCoA desaturase. Moreover, an FP receptor agonist, Fluprostenol, suppressed the expression of those adipogenic genes in 3T3-L1 cells; whereas an FP receptor antagonist, AL-8810, efficiently inhibited the suppression of adipogenesis caused by the endogenous PGF 2␣ . These results indicate that AKR1B3 acts as the PGFS in adipocytes and that AKR1B3-produced PGF 2␣ suppressed adipocyte differentiation by acting through FP receptors.

A superconducting joint technology used for high-temperature superconductors (HTS) is the key for enabling persistent operation of HTS magnets. In the present work, we have succeeded in developing a superconducting joint between REBCO-coated conductors (CCs) using a joint strap with a microcrystalline GdBCO precursor intermediate layer. Heat treatment and oxygen annealing, with a total processing time of less than 1 d, grows a biaxially-textured intermediate layer to connect the GdBCO layers in the CCs. Microstructure observation of a part of the joint cross-section with SEM and TEM showed that the intermediate layer and the GdBCO layers in the conductors were atomically connected. An electron backscatter diffraction result showed that both the c- and a-axis misorientations among the GdBCO layers of the joined conductor and the GdBCO layer of the joint strap were about less than 5°. This intermediate grown superconducting joint gives a critical current of >100 A at 77 K in a self-field. A critical current of a joint at 4.2 K in a self-field is seven times higher than that at 77 K. The persistent field decay of a small double pancake coil, terminated with this joint, showed a joint resistance in the range of <3 × 10−12 Ω to <5 × 10−13 Ω at 77 K in a self-field over three days, with an operating current of ∼10 A (∼14% of the calculated coil critical current). The results show a promising prospect of the joint to be used for persistent magnets such as NMR and MRI.

Prostaglandin (PG) F 2a suppresses adipocyte differentiation by inhibiting the function of peroxisome proliferator-activated receptor c. In this study, we identified a novel suppression mechanism, operating in the early phase of adipogenesis, that increased the production of anti-adipogenic PGF 2a and PGE 2 by enhancing cyclooxygenase (COX) 2 expression through the PGF 2a -activated FP receptor ⁄ extracellular-signal-regulated kinase (ERK) ⁄ cyclic AMP response element binding protein (CREB) cascade. COX-2 expression was enhanced with a peak at 1 h for the mRNA level and at 3 h for the protein level after the addition of Fluprostenol, an FP receptor agonist. The Fluprostenol-derived elevation of COX-2 expression was suppressed by the co-treatment with an FP receptor antagonist, AL8810, with a mitogen-activated protein kinase (MEK; ERK kinase) inhibitor, PD98059. ERK was phosphorylated within 10 min after the addition of Fluprostenol, and its phosphorylation was inhibited by the co-treatment with AL8810 or PD98059. Moreover, FP receptor mediated activation of the MEK ⁄ ERK cascade and COX-2 expression increased the production of PGF 2a and PGE 2 . An FP receptor antagonist and each inhibitor for MEK and COX-2 suppressed the PGF 2a -derived induction of synthesis of these PGs. Furthermore, promoter-luciferase and chromatin immunoprecipitation assays demonstrated that PGF 2a -derived COX-2 expression was activated through binding of CREB to the promoter region of the COX-2 gene in 3T3-L1 cells. These results indicate that PGF 2a suppresses the progression of the early phase of adipogenesis by enhancing the binding of CREB to the COX-2 promoter via FP receptor activated MEK ⁄ ERK cascade. Thus, PGF 2a forms a positive feedback loop that coordinately suppresses the early phase of adipogenesis through the increased production of anti-adipogenic PGF 2a and PGE 2 .

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