Retinoic acid (RA) receptors (RARs) are nuclear receptors that play a critical role in regulating cellular proliferation, development and differentiation in vertebrates in response to endogenous RAs, i.e., all-trans RA and 9-cis RA. On the other hand, it has been well-known that both a deficiency and an excess of RA and related retinoids can cause a variety of teratogenic effects on developing embryos of vertebrates, which has been proven to be an -mediated process. Therefore, the occurrence of xenobiotic environmental pollutants that interfere with RARs and disrupt the signaling (i.e., show agonistic or antagonistic effects) may pose a threat to the health of wild animals and humans. This review mainly focuses on agonists. We summarize the agonistic activity of natural and xenobiotic compounds determined using in vitro bioassay systems and present recent field research showing the occurrence of agonist contamination in the aquatic environment in North America, China and Japan. Environmental pollution by agonists is a new endocrine disruption issue discovered very recently, and relevant knowledge is very limited. Further research will be required to obtain accurate information to assess the possible risks of agonists in the environment.

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The mechanism of the recto-anal reflex (), i.e, transient fall of anal canal pressure induced by rectal distension, is still obscure. In order to elucidate the role of the sacral nerves to ., the effects of denervation and stimulation of the sacral nerves were examined experimentally in dogs. A laminectomy was done to expose the sacral nerve roots in each dog. Each and/or all sacral nerves were tied and devided or stimulated extradurally. In chronic experiments, was examined repeatedely over two weeks after operation. was not obtained when all sacral nerves were devided, but when any indivisual sacral nerve was remained undivided, was elicited in all dogs. In acute experiments, electrical stimulation of the sacral nerve (especially S_1 and S_2) brought about a transient fall of the anal canal pressure and a marked inhibition of sustained electrical activity of the internal anal sphincter muscle. Both were identically seen in pressure and muscle while the rectum was distended by a balloon. The results indicate that the recto-anal reflex is dependent not only on the intramural pathway but also on the sacral nerve pathway when this reflex action is elicited in a physiological condition.

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Experimental studies are carried out on the heat transfer of open circular thermosyphons (the radius of length to radius are 6 and 10) using liquid sodium. The Nusselt numbers (N_ur) measured for liquid sodium are plotted against the Rayleigh number () and the product of the and Prandtl number (P_r). These results cover a range of from 4×10² to 1.7×10⁵ or from 10 to 9.5×10³ and are compared to the previous results of mercury. It is shown that the arrangement of N_ur against is more appropriate than that against . The heat transfer of open thermosyphons for liquid sodium and mercury shows similar characteristics. The effect of convection flow on N_ur becomes significant over about 60 .

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Obesity is characterized by an excessive accumulation of fat and associated with various metabolic diseases. Recently, conversion of white adipocytes to brown-like adipocytes (beige adipocytes), naming browning has been focused as an attractive therapeutic strategy for the treatment of obesity. In the present study, we found that adapalene, a retinoic acid (RA) analogue that is often used as an anti-acne drug, induces adipose browning. Adapalene concentration dependently increased mRNA and protein expressions of browning markers including uncoupling protein-1 (UCP-1) in fully differentiated 3T3-L1 white adipocytes and in murine primary adipocytes. In agreement with increased expression of browning markers, reduced lipid droplets, and increased oxygen consumption rates and mitochondrial biogenesis were detected upon adapalene treatment. Conversely, knockdown of RARs by siRNAs attenuated adapalene-induced browning, suggesting that adapalene-induced browning is associated with

activation. In vivo browning effect of adapalene was confirmed using C57BL/6J mice. In summary, these data suggest that adpalene induces browning of white adipocytes via activation, implying its possible new application as an anti-obesity drug.

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We previously reported that ER-27191 (4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid) is a potent antagonist of retinoic acid receptor (), and ER-35795 ((2E,4E,6E)-7-[1-(1-methylethyl)-8-chloro-1,2,3,4-tetrahydroquinolin-6-yl]-6-fluoro-3-methyl-2,4,6-nonatrienoic acid) is a novel retinoid X receptor (RXR)-specific agonist. By using these compounds, we investigated whether distinct -dependent and RXR-dependent pathways operate to mediate the diverse activities of retinoids, particularly, the effects of the RXR pathway on cellular function. ER-27191 completely antagonized HL60 cell differentiation induced by all-trans-retinoic acid (atRA). However, the differentiation induced by the ER-35795 was not antagonized at all by the antagonist, but was inhibited by an RXR homodimer antagonist (LGD100754, (2E,4 E,6Z)-7-(3-n-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid). Its agonistic action on RXR/ heterodimer, on the other hand, was neutralized by the antagonist. During HL60 cell differentiation, atRA induced RARβ mRNA, while the RXR had no effect. Interestingly, a functional RXR-pathway was also seen in lipopolysaccharide-induced inhibition of mouse splenocyte proliferation. These results strongly suggest the existence of a pharmacological RXR-dependent pathway that is activated by a ligand that can bind to RXR.

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Retinoids (retinoic acid and its analogs) are widely involved in the control of cell proliferation, cell differentiation and embryonic development. A series of potent and novel synthetic retinoids named retinobenzoic acids has been developed. Retinobenzoic acids have proven to be useful tools in the investigation of the molecular mechanisms of retinoidal actions. Retinoids elicit their biological effects by binding to and activating specific nuclear receptors for retinoids ('s) which belong to the steroid/thyroid nuclear receptor superfamily. Recent investigations concerning the structure and function of nuclear receptors, namely of 's, are reviewed. Three subtypes of (-α, -β and -γ) have been identified so far. Each is considered to play particular roles in the retinoidal actions. The role of each is discussed in relation to their features and to the structure-activity relationships of retinoids. 's act as retinoid-dependent transcription factors which bind to a specific site of the gene and control its expression. Recent progress in the investigation of the interaction of 's with the responsive genes and with nuclear co-factors is reviewed. The diversity of retinoidal actions are possibly explained by the diversity of 's in their structure and in their spatial and temporal distribution, by the diversity of base sequences which interact with 's, by the diversity of cell type-specifically determined hierarchy of gene expression, and by the diversity of the nuclear factors which interact with 's.

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 An operational real-time adjusted radar-automatic weather station (AWS) rain rate (RAD-) system, using 10 radars of the Korea Meteorological Administration (KMA), has been developed for the South Korea region. The procedure of the RAD- system consists of four steps for real-time operation: 1) the quality control of volumetric reflectivity for each radar, 2) the computation of the rain-gauge rain rate every 10 min. within each radar, 3) the real-time (updated every 10 min.) rainfall estimation by the Z-R relationship minimizing the difference between the 10-min constant altitude plan position indicator and rain-gauge rain rate based on window probability matching method (WPMM) and by the real-time bias correction of RAD- conducted at 10 min. intervals for each radar by making the bias, and 4) the composition of estimated rainfall data of the 10 radars. It is noted that this RAD- system is available only for summer rainfall cases with the absence of bright band around 1.5 km in height, as the system does not include bright band correction. The performance of RAD- was examined for the 10 heavy rainfall events of 2006, and we obtained results suggesting that the real-time Z-R adjustment of RAD- is better in terms of the agreement with the rain-gauge rain rate than that of the previously fixed Z-R relationship, and the additional bias correction of RAD- yields slightly better results. A square of correlation coefficient R²=0.84 was obtained between the daily accumulated observed and RAD- estimated rainfall.

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We investigated robot-assisted recreation (

) for improving the quality of life (QoL) of older adults with dementia in an aged care facility. However, as a simple method to evaluate has not been established at the field level, limited scientific data exists to show its effectiveness. To solve this problem, we studied a method to evaluate based on speech analysis, which can reduce the burden on subjects (older adults) and data analysts. This study conducted both subjective and objective analyses of speech data. Subjective analysis based on the transcripts of speech data resulted in findings that supported and added to the knowledge of previous research, such as an increased willingness to participate in , positive feelings toward the future, and interest in interacting with others. The results of the objective analysis based on the fundamental frequency (F0) demonstrated that there was a difference in the distribution of F0 during and the interviews conducted before and after . This study thus provides the prospect for easy evaluation of recreational activities, including , in aged care facilities at the field level using speech analysis.

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Retinoic acid (RA) regulates the growth of human salivary gland adenocarcinoma cell line (HSG), through mediation of a retinoic acid receptor (

) expressed in the nuclei of HSG cells. In the process of induction of biological effects of , the binding of to a retinoic acid response element (RARE) on the promoter of the target gene is essential.

In this study, we first examined the DNA binding properties of the in vitro-transcribed and -translated human

α and RXR α, retinoid X receptor α/9-cis α, using a gel-mobility- shift assay. Then, the DNA binding ability of the nuclear extract of HSG cells was investigated in vitro to examine whether expressed in HSG cells has a biological function.

In vitro-translated RARαor RXRαdid not bind to [γ-³²P] ATP-labeled β RARE, a naturally occurring RARE found on the 5’-promoter of

β. However, α bound to [³²P] β RARE in the presence of RXR α, suggesting that α requires RXR α as a coregulator when it binds to β RARE. The binding was competed by an excess amount of unlabeled β RARE but not by a glucocorticoid response element (GRE), indicating that the binding was specific.

On the contrary, the nuclear extract of HSG cells bound to [³²P] β RARE by itself, and the binding was found to be specific in competition analysis using an excess amount of unlabeled β RARE and GRE. When the anlount of the nuclear extract used for the binding was increased, the band was broadened, indicating the heterogeneity of the binding.

These findings suggest that the nuclear extract of HSG cells contain molecules belonging to the RXR family, and these molecules cooperate with

of HSG cells in the process of transactivations which induce various biological functions of .

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植物の抵抗性(Resistance;R)蛋白質は病原菌由来のエフェクターを認識し、過敏感反応と称される強い抵抗性反応を誘導する。一方、動物の自然免疫においてもR蛋白質のホモログであるNod like proteins(NLPs)が病原菌の認識を担っている。これまでの研究によって、1-SGT1-HSP90複合体がR蛋白質の安定化に必須な役割を果たすこと、さらにSGT1-HSP90複合体が動物のNLPsの安定化と活性化に必須であることが示された。我々はこの複合体の立体構造解析及び機能解析を行い、1及びHSP90と結合するSGT1のCSドメインの立体構造とSGT1-HSP90複合体の部分立体構造を解明した。さらに最近、1、SGT1及びHSP90の各ドメインを含む複合体の立体構造解明に成功した。立体構造情報をもとに生化学、分子生物学的解析を行ったところ、(1)1はSGT1及びHSP90と直接結合することにより複合体形成を促進すること、(2) SGT1は1と結合することにより、R蛋白質との結合親和性を増大することが分かった。また、部位特異的変異導入により、1とSGT1の結合を阻害すると上記の変化が起こらないだけでなく、病原体に対する抵抗性も低下した。このことから、1とSGT1の結合が複合体形成、及び抵抗性反応の誘導に必須であることが明らかとなった。

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正常ヒト皮膚におけるレチノイン酸受容体（）遺伝子の発現パターンを，-α，-β，-γのcDNAより作製したリボプロープを用い，in situ hybridization法により解析した．-αおよび-γ遺伝子は表皮に特異的に発現していたが，-β遺伝子は表皮にも真皮にもほとんど発現していなかった．-αと-γ遺伝子は表皮の基底細胞層，有棘細胞層のいずれにおいても発現しており，両遺伝子の発現パターンに明らかな差異を見いだせなかった．さらに，-αおよび-γ遺伝子はエクリン汗腺においても発現していた．以上の結果は，ヒト皮膚において表皮ケラチノサイトおよび附属器上皮細胞がレチノイン酸の標的細胞であることを示すとともに，ケラチノンサイトおよび附属器上皮細胞の分化調節に，のサブタイプのうち-αと-γが関与していることを示唆している．

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We have proposed Robot Assisted Rehabilitation () in which stimulative impression of robots produces effective rehabilitation. In , mental and social effects are expected in addition to physical effect. With these three effects in mind we have done in the nursing home for the aged and the rehabilitation ward. In this paper, we report trial practices using commercially available entertainment robots in remote operation mode.

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We have shown that OsRac1, a rice Rac GTPase, is involved in innate immunity. In this study we examined the functional relationships between OsRac1, and 1 and HSP90, two important components of R gene-mediated disease resistance. OsRAR1-RNAi plants had impaired basal resistance to the blast fungus and the virulent bacterial blight. Constitutively active OsRac1 complemented the loss of resistance, suggesting that OsRac1 and OsRAR1 are functionally linked. Co-immunoprecipitations indicate that OsRac1 forms a complex with 1 and HSP90 in vivo. Studies with OsRAR1-RNAi and geldanamycin, a HSP90 specific inhibitor, showed that 1 and HSP90 are essential for the OsRac1-mediated immune responses. Furthermore, the function of HSP90, but not 1, is essential for their association with OsRac1. OsRac1 also regulates expression at both the mRNA and protein levels. Together, our results indicate that OsRac1, OsRAR1 and HSP90 form one or more complexes and play important roles in rice innate immunity.

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Low (reducing agent rate) operation of the blast furnace is one of effective techniques for reducing CO₂ emissions. Coke mixed charging is a well-known and available measure to achieve low operation by improving permeability and reducibility. Utilization of hydrogenous reducing agents is also an efficient measure. A reduction test under load was performed to investigate the effect of coke mixing with hydrogen addition on reduction behavior of the ore. Simultaneous use of coke mixing and hydrogen addition accelerated the reduction rate through the carbon gasification rate, and it was also decreased pressure drop. The effect of coke mixing and hydrogen addition on blast furnace operation was examined using a two-dimensional mathematical simulation model. In case of the ore layer mixed with coke, hydrogen addition in the reduction gas increased the hydrogen reduction ratio and decreased the direct reduction ratio. As a result, decreased and permeability improved.

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is a CHORD-containing gene and essential for Rgene-mediated resistance in plants. In addition to , small GTPase Rac family was also found to play an important role in disease resistance in rice. Immunoprecipitation (IP) assay indicated that OsRac1 and 1 existed in the same complex. To study the function and relationship between OsRac1 and OsRar1 in rice disease resistance we used OsRac1-RNAi and CA-OsRac1 transgenic plants for genetic analysis. Results of plant infection assays suggest that OsRar1 contributes to basal resistance, whereas lack of OsRar1did not alter Pi-a, Pi-b and Pi-z mediated resistance. OsRac1 and OsRar1 may function in parallel pathways, OsRar1 silencing impairs the basal resistance, however overexpressing CA-OsRac1 can compensate the loss of OsRar1 function. Yeast two hybrid assay indicated that OsRar1, OsSgt1 and HSP90 may form a scaffold of a big complex. OsRac1 may exist in this complex but not directly associate with the scaffold.

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Nuclear retinoic acid receptors RARα, RARβ and RARγ are transcription factors that bind all-trans retinoic acid as their ligand and mediate its action by activating particular set of genes that contain retinoic acid responsive elements in their promoter-enhancers. We have mapped genetic loci for these genes using restriction fragment length variants (RFLVs) in interspecific backcross mice. None of the loci cosegregated with each other or with the new subclass of retinoid receptors, Rxr loci. Rara mapped to mChr 11, Rarb mapped to mChr 14, and Rarg mapped to mChr 15. The results are consistent with the previous reports and the human data in terms of syntenic homology between mouse and human chromosomes.

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Low reducing agent rate () operation of blast furnace is a key technology to reduce carbon dioxide emission from the steel industry. To realize stable and highly effective operation of blast furnace under low condition, permeability in the furnace has to be kept in sufficient level. Keeping bed permeability is an essential issue in blast furnace operation especially from the viewpoint of prospective change in circumstance of raw material resources. This paper focuses on powder behavior that deteriorates bed permeability in blast furnace. It is known that excessive accumulation of powder in the burden bed causes serious operation troubles like slip, hanging and so on, therefore the powder accumulation should be suppressed as little as possible. To suppress powder accumulation it is necessary to understand the powder behavior in packed bed, thus this paper summarizes three mechanisms of powder formation, flow and accumulation in blast furnace. Regarding powder generation, numerous research works on ore degradation with progress of reduction, un-burnt char formation in raceway zone and coke degradation have been made and revealed their characteristics in detail. As for powder flow and accumulation, their macroscopic characteristics have been elucidated. It is expected that the profiles of temperature, gas concentration and material flows in the blast furnace under low operation is drastically different from the ones under current operating conditions. Thus further discussions taking into account such differences in conditions and microscopic viewpoints are required for comprehensive understanding of powder behavior under low blast furnace operation.

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レチノイン酸（RA）の結合を介して形態形成等の制御を担っているRA受容体（）は，そのシグナル伝達の過剰発現により催奇形性作用をもたらす可能性がある。これまでの研究から，下水中にはアゴニストが常に存在し，その主要物質がall-trans RA（atRA），13-cis RA（13cRA），4-oxo-atRA，および4-oxo-13cRAであることが特定された。本研究では，これら4物質の下水処理過程における挙動の解明を目的として，都市下水処理場における4物質の挙動とアゴニスト活性の推移を調査した。その結果，RA類と4-oxo-RA類は，時季や処理方式によらず，活性汚泥処理によって良好に除去されることが明らかとなり，処理過程で未知のアゴニストが生成する可能性もあるが，現在の放流水のアゴニストレベルでは水生生物に対して直ちに生体影響が生じる可能性は低いと考えられた。

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