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The potential impact of postdispersal seed predation by the field cricket, Teleogryllus emma (Ohmachi et Matsuura), on the seedling emergence of Italian ryegrass (Lolium multiflorum Lam.), a non-native grass weed in Japan, was determined. The relationship between cricket density and the proportion of seedling emergence was investigated by conducting manipulative experiments in duplicate, using enclosures. One-thousand seeds of Italian ryegrass were exposed to adult crickets at different densities (zero, one, two, four and eight individuals per 2.25 m2 enclosure) for 2 weeks. The proportion of seedling emergence decreased with increasing cricket density. The proportion of seedling emergence in the enclosures without the crickets was 90.9–97.2%, whereas the seedling emergence in the enclosures with eight crickets greatly decreased, to 0.5–2.5%. These results suggest that postdispersal seed predation by T. emma can substantially decrease the abundance of Italian ryegrass at an early life stage and reduce its population in environments with a high density of crickets.

Induced circular dichroism (ICD) was observed in binaphthyl N -methyl amides of chiral primary amines. The CD spectra showed split curves centered at 225 nm. A good correlation was found between the sign of the exciton chirality of the binaphthyl derivative and the absolute configuration of the original amine. Furthermore, the screw sense of the two naphthyl groups in the most stable conformer obtained from molecular mechanics (MM) calculation was in agreement with those expected from the exciton chirality, indicating that the method based on MM calculations can be used to determine unknown absolute configurations of aliphatic chiral amines. The practical use of the present method was demonstrated by the determination of the absolute configurations of the natural products, d - and l -cycloserines.

A series of benzo[b]furan derivatives having a five-membered heterocyclic substituent at the 2-position were prepared from 2-(1-chloro-2-formylvinyl)benzo[b]furans (2) and 2-(4-alkylcarbamoylbuta-1,3-dienyl)benzo[b]furans. These 2-heterocyclic benzo[b]furans were evaluated for their cysteinyl leukotriene receptor (cysLT1, cysLT2) inhibitory activity. Several compounds showed moderate inhibition of calcium mobilization in HEK 293T-cysLT2 or CHO-cysLT1 cells.

Various toughened-material systems to reinforce interlaminar strength of CFRP have been proposed on the basis of the results of coupon tests. In this paper, an applicability of toughened-material systems to structural model such as curved beam subject to static bending was examined. Two kinds of CFRP with different toughened-material system were selected, and both microscopic observation and numerical FEM simulation using VCCT were performed for test results. A difference between coupon and structural model tests was found for the case of the curved beam with artificial anomaly, and the cause was considered due to the difference of delamination pass between coupon and curved beam tests. From a view point of numerical simulation for predicting the strength behavior of the curved beam, an adoption of different fracture toughness from that by coupon test was necessary.

Telomerase reverse transcriptase (TERT) contributes to the prevention of aging by a largely unknown mechanism that is unrelated to telomere lengthening. The current study used ataxia-telangiectasia mutated (ATM) and TERT doubly deficient mice to evaluate the contributions of 2 aging-regulating molecules, TERT and ATM, to the aging process. ATM and TERT doubly deficient mice demonstrated increased progression of aging and had shorter lifespans than ATM-null mice, while TERT alone was insufficient to affect lifespan. ATM-TERT doubly null mice show in vivo senescence, especially in hematopoietic tissues, that was dependent on p16INK4a and p19ARF, but not on p21. As their HSCs show decreased stem cell activities, accelerated aging seen in these mice has been attributed to impaired stem cell function. TERT-deficient HSCs are characterized by reactive oxygen species (ROS) fragility, which has been suggested to cause stem cell impairment during aging, and apoptotic HSCs are markedly increased in these mice. p38MAPK activation was indicated to be partially involved in ROS-induced apoptosis in TERT-null HSCs, and BCL-2 is suggested to provide a part of the protective mechanisms of HSCs by TERT. The current study demonstrates that TERT mitigates aging by protecting HSCs under stressful conditions through telomere length-independent mechanisms.

Neural progenitor cells and developing neurons show periodic, synchronous Ca2+ rises even before synapse formation, and the origin of the synchronous activity remains unknown. Here, fluorescence measurement revealed that the membrane potential of the nuclear envelope, which forms an intracellular Ca2+ store, changed with a release of Ca2+ and generated spontaneous, periodic bursts of fluctuations in potential. Furthermore, changes in the nuclear envelope’s potential underlay spike burst generations. These results support the model that voltage fluctuations of the nuclear envelope synchronize Ca2+ release between cells and also function as a current noise generator to cause synchronous burst discharges.

The extent of post-dispersal weed seed predation in upland wheat fields converted from paddy fields was quantified in Shizuoka Prefecture, central Japan. We investigated the temporal variability in seed predation of Italian ryegrass (Lolium multiflorum Lam.), a non-native winter annual weed in Japan, during summer after the seed shed in both the field interior areas and boundary strips, and estimated the total seed loss due to predation during the summer. Furthermore, the contribution of invertebrates and vertebrates to seed predation was estimated by using exclosures. The total seed loss due to predation during four months (from late June to late October) in the field interior areas and boundary strips was estimated to be 35–43% (the maximum proportion of seed predation per two weeks = 27%) and 42% (25%), respectively. The seed predators in the field interior areas were vertebrates (rodents or birds) and invertebrates (crickets and ground beetles). In contrast, seed predators in the boundary strips were mainly invertebrates (crickets and ground beetles). The results of this study suggest that predators make a substantial contribution in the depletion of post-dispersal seeds of Italian ryegrass in converted paddy fields.

Neotyphodium endophytes often confer benefits to their host grasses and may enhance invasiveness of some grasses. The knowledge of infection frequencies of endophytes among invading weed populations is necessary to understand the relationships between endophyte infection and invasiveness. Here we present data on infection frequencies of Italian ryegrass (Lolium multiflorum Lam.), an important weed in some farmlands in Japan, persisting in contrasting farmlands: a terraced paddy field and a wheat-soybean double-cropped field in the western region of Shizuoka prefecture, Japan. The terraced paddy site is a mosaic of several landscape elements such as paddy fields, levees, fallow and abandoned fields, with a high percentage of non-crop area. Rice (Oryza sativa L.) has been cultivated for more than a decade with no application of chemical fertilizers, pesticides and fungicides. The wheat-soybean field is characterized by the aggregation of large-scaled fields that were originally reconstructed paddy fields, showing a low percentage of non-crop area. Wheat and soybean have been grown as winter and summer crops, respectively, using chemical fertilizers and herbicides. We examined the presence or absence of endophytes in a total of 1200 seeds sampled from the two Italian ryegrass populations. The terraced paddy population exhibited a markedly high infection frequency (91.0%), due possibly to selective feeding of non-infected seeds by insects. In contrast, the wheat-soybean farmland population showed almost no infection (1.1%), whereas the putative source of the invasion in the proximity exhibited a relatively high infection rate (64.4%). Such a micro-scale variation in infection frequencies may be attributable to a loss in endophyte viability within the wheat-soybean field. The findings suggest that endophyte infection frequency may markedly differ among the Italian ryegrass populations even within the same region, presumably depending on the abundance of the seed-eating insects, farmland management regimes and/or environmental conditions such as soil humidity.

コムギ圃場におけるネズミムギ発生量とコムギ減収率との関係を迅速かつ簡易に把握するため，達観調査による簡易査定法を開発した。コムギとダイズを連作する静岡県袋井市豊住の水田転作団地を調査対象とし，2004年∼2007年のコムギ収穫時期に圃場別にネズミムギ発生量の達観調査を行った。達観調査による査定基準は「無」，「微」，「少」，「中」，「多」，「甚」の6段階とした。査定したランク別にコムギ収量，ネズミムギ個体数，全乾物重をコドラート（1m×1m）調査した。達観調査に基づく査定ランクごとにネズミムギの発生量（個体数と全乾物重）に明瞭な差があり，コムギの減収率を概ね適正に評価していた。コドラート内のネズミムギの個体数が多く，乾物重が大きいほど，コムギ精子実重の減収率が高く，その関係は方形双曲線モデルにより回帰できた（R2>0.6）。20%以上のコムギ減収が生じるネズミムギの密度は8∼12個体/m2以上であった。達観調査による簡易査定法は，地域レベルでの雑草発生量，コムギ減収量を迅速に推定する上で有効である。

Chronic inflammation is associated with bone marrow (BM) failure, aging and hematological malignancies. TNFα is a major pro-inflammatory cytokine overproduced in many hematological diseases, which is also known as a prototypical death ligand that can trigger programmed cell death in effector cells. Hematopoietic stem cells (HSCs: Lin-cKit+Sca1+Flk2-CD48-CD150+) are highly responsive to an altered cytokine milieu in the BM, and show unique response to cell death stimuli compared to downstream progenitors. Yet, how TNFα regulates HSCs and downstream progenitors remains controversial. In vitro treatment with TNFα revealed that HSCs were totally resistant to TNFα-induced cell death regardless of the dose (1 ng/ml ~ 10 μg/ml) in cytokine-rich conditions, although they become somewhat susceptible in cytokine-poor conditions, in contrast to granulocyte-macrophage progenitors (GMPs: Lin-cKit+Sca1-FcγR+CD34+) that were killed by TNFα exposure in both conditions. Mechanistically, TNFα induced a stronger activation of canonical NF-κB in HSCs than GMPs, with higher NF-κB-GFP reporter activity and more robust nuclear translocation of p50 and p65. Pharmacological blockade of canonical NF-κB with the IKKβ inhibitor BMS-345541 rendered HSCs partially susceptible to TNFα-induced cell death, while deficiency for p65, but not p50, resulted in complete HSC susceptibility to TNFα-mediated cell killing. Remarkably, we discovered that necroptosis, but not apoptosis, was the dominant cell death pathway in HSCs that had partial blockade of canonical NF-κB. HSCs with kinase-inactive RIPK1, RIPK3 deficiency or MLKL deletion all exhibited complete resistance to TNFα-mediated killing in IKKβ inhibited conditions, whereas HSCs deficient for caspase-8, BID, or BAK/BAX showed comparable susceptibility. In contrast, complete blockade of NF-κB through p65 deletion activated both apoptosis and necroptosis pathways, and could only be rescued by treatment with a combination of the pan-caspase inhibitor zVAD-fmk and RIPK1 inhibitor GSK'963. By contrast, TNFα-induced GMP death could not be rescued by either apoptosis or necroptosis inhibition, or a combination of both. To gain more insights into the molecular mechanism driving the differential response to TNFα, we performed RNA-seq-based whole transcriptome analyses of HSCs and GMPs treated with TNFα either in vitro or in vivo. We extracted cell-specific signatures of TNFα exposure in HSCs (62 genes) and GMPs (51 genes), which correspond to genes upregulated across all types of TNFα treatment (FDR3-fold). Notably, we identified cIAP2, a critical regulator for pro-survival effect in TNFα pathway, as one of the 44/62 unique genes upregulated in TNF-exposed HSCs. Quantitative RT-PCR analyses confirmed that TNF-exposed HSCs upregulate cIAP2 in a p65-dependent manner, and treatment with the cIAP inhibitor LCL-161 completely sensitized HSCs to TNFα-induced cell death even with intact p65 nuclear translocation. By contrast, TNFα-exposed GMPs showed a signature of cell death pathway activation and pro-inflammatory mediators. Finally, we investigated the effect of TNFα on hematopoiesis in vivo. Intravenous injection with TNFα (3x 2 μg every 12 hours, harvest 24 hours later) significantly reduced the absolute number of GMPs, but not HSCs. Importantly, canonical NF-κB was quickly activated in HSCs upon each TNFα injection but was desensitized 24 hours later. As a consequence, we observed a striking reduction in engraftment capacity of TNFα-exposed HSCs that was due in large part to necroptosis killing resulting from NF-κB desensitization, and was rescued by RIPK3 deficiency. Strikingly, chronic inflammation induced by repeated poly I:C injections (7x 10 mg/kg every 2 days) increased TNFα production and lead to NF-κB activation in HSCs. This was completely abrogated in HSCs isolated from poly I:C-treated TNFα-deficient mice, suggesting that TNFα is the major source of NF-κB activation in HSCs during chronic inflammation. As a result, we observed significant loss of HSC numbers in poly I:C-treated TNFα-deficient mice, which was completely rescued by RIPK3 deficiency. Taken together, our results demonstrate that HSCs are protected by TNFα-dependent canonical NF-κB activity from necroptosis during inflammation, which has significant implications for the treatment of patients with hematological malignancies and compromised NF-κB signaling. Disclosures No relevant conflicts of interest to declare.

Increases in intracellular [Ca2+] occur synchronously between cells in the neuroepithelium. If neuroepithelial cells were capable of generating action potentials synchronized by gap junctions (direct current electrical coupling), the influx of Ca2+ through voltage-activated Ca2+ channels would lead to a synchronous increase in intracellular [Ca2+]. However, no action potential is generated in neuroepithelial cells, and the [Ca2+] increase is instead produced by the release of Ca2+ from intracellular Ca2+ stores. Recently, synchronous fluctuations in the membrane potential of Ca2+ stores were recorded using an organelle-specific voltage-sensitive dye. On the basis of these recordings, a capacitative [alternating current (AC)] electrical coupling model for the synchronization of voltage fluctuations of Ca2+ store potential was proposed [Yamashita M (2006) FEBS Lett580, 4979–4983; Yamashita M (2008) FEBS J275, 4022–4032]. Ca2+ efflux from the Ca2+ store and K+ counterinflux into the store cause alternating voltage changes across the store membrane, and the voltage fluctuation induces ACs. In cases where the store membrane is closely apposed to the plasma membrane and the cells are tightly packed, which is true of neuroepithelial cells, the voltage fluctuation of the store membrane is synchronized between the cells by the AC currents through the series capacitance of these membranes. This article provides a short review of the model and its relationship to the structural organization of the Ca2+ store. This is followed by a discussion of how the mode of synchronization of [Ca2+] increase may change during central nervous system development and new molecular insights into the synchronicity of [Ca2+] increase.

Italian ryegrass (Lolium multiflorum Lam.) is an exotic winter annual weed that recently has seriously infested wheat fields in central Japan. To understand the influence of tillage systems on the germination ecology and seedbank dynamics of naturalized Italian ryegrass, we compared the fate of the seeds that were after-ripened in the soil with that of the seeds on the soil surface, and then examined the germination characteristics of the seeds retrieved from both treatments by germination tests in both a light/dark (12 h photoperiod) condition and in constant darkness. The seedling emergence was greater initially for the seeds after-ripened on the soil surface than for the seeds in the soil. The component of emergent seeds after-ripened on the soil surface increased as time passed during the summer, whereas that of emergent seeds in the soil scarcely increased. This contrasting emergence was, in part, attributable to the ability of the seeds to germinate at higher temperatures in the light/dark condition than in constant darkness. These results suggest that untilled systems, which leave many seeds on the soil surface, might promote the rapid depletion of Italian ryegrass seeds through germination before wheat sowing in early winter. In contrast, seed burial by tillage might inhibit the germination of the seeds and form a large transient seed bank available to germinate during the wheat-growing season.

近年，静岡県中遠地域の水田転換コムギ圃場で問題となっているネズミムギの防除法の確立を目的とし，ダイズ作とコムギ作における耕起，不耕起の管理体系の違いがネズミムギの出芽に及ぼす影響について調査を行った。 ダイズ作の不耕起栽培によって，慣行の耕起栽培に比してコムギ播種前のネズミムギの出芽数が増加したが，コムギ作におけるネズミムギの出芽数の減少は認められなかった。コムギ作におけるネズミムギの出芽数は，ダイズの耕起栽培とコムギの不耕起栽培の組み合わせで最も少なかった。コムギ不耕起条件では，コムギ播種後の土壌硬度が固く，ネズミムギ出芽深度は土壌浅層に偏った。重粘土壌におけるダイズ作耕起栽培とコムギ不耕起栽培の組み合わせは，夏期に土壌表層のネズミムギ種子を出芽可能深度以下の土中深層に埋没させ，その後の不耕起により埋没した種子の出芽を抑制できると考えられる。

Synchronous Ca2+ oscillation occurs in various cell types to regulate cellular functions. However, the mechanism for synchronization of Ca2+ increases between cells remains unclear. Recently, synchronous oscillatory changes in the membrane potential of internal Ca2+ stores were recorded using an organelle-specific voltage-sensitive dye [Yamashita et al. (2006) FEBS J273, 3585–3597], and an electrical coupling model of the synchronization of store potentials and Ca2+ releases has been proposed [Yamashita (2006) FEBS Lett580, 4979–4983]. This model is based on capacitative coupling, by which transient voltage changes can be synchronized, but oscillatory slow potentials cannot be communicated. Another candidate mechanism is synchronization of action potentials and ensuing Ca2+ influx through voltage-dependent Ca channels. The present study addresses the question of whether Ca2+ increases are synchronized by action potentials, and how oscillatory store potentials are synchronized across the cells. Electrophysiological and Ca2+-sensitive fluorescence measurements in early embryonic chick retina showed that synchronous Ca2+ oscillation was caused by releases of Ca2+ from Ca2+ stores without any evidence of action potentials in retinal neuroepithelial cells or newborn neurons. High-speed fluorescence measurement of store membrane potential surprisingly revealed that the synchronous oscillatory changes in the store potential were periodic repeats of a burst of high-frequency voltage fluctuations. The burst coincided with a Ca2+ increase. The present study suggests that synchronization of Ca2+ release is mediated by the high-frequency fluctuation in the store potential. Close apposition of the store membrane and plasma membrane in an epithelial structure would allow capacitative coupling across the cells.

Introduced Lolium species, including perennial ryegrass (Lolium perenne) and Italian ryegrass (Lolium multiflorum), have been widely utilized in Japan for forage, turf and soil conservation. These ryegrasses have escaped from cultivated areas and become naturalized, and this has become a serious issue in recent years. Interspecific hybrids between perennial ryegrass and Italian ryegrass have often been found in naturalized populations. It has also been suggested that hybridization between plant species might serve as a stimulus for the evolution of invasiveness. We surveyed the genetic structure of naturalized ryegrass populations in Japan using genetic markers that distinguished perennial ryegrass and Italian ryegrass. Of the 55 naturalized populations surveyed, 41 exhibited morphological traits of Italian ryegrass. DNA analysis using simple sequence repeat and chloroplast DNA markers characterized 20 of these 41 populations as Italian ryegrass, with the remaining populations as interspecific hybrid derivatives. Approximately half of the naturalized ryegrasses populations in Japan were inferred to include interspecific hybrids.

When 1-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones (1) were treated with dimethylsulfoxonium methylide, 1-endo isomers (endo-1) gave 1-substituted 3-aroyl-1,2,4a,9b-tetrahydrodibenzofuran-4-ols (2) exclusively as expected. On the other hand, 1-exo isomers (exo-1) underwent a novel transformation to 1-substituted 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans (3), together with 2.

The novel skeleton transformation reaction of 2a-substituted 2a,8b-dihydrobenzo[ B]cyclobuta[ D]pyran-3-one derivatives into 2-(2-substituted 2-oxoethyl)-2 H-1-benzopyran derivatives has been accomplished using Znl 2 in the presence of an organic base and water in excellent yields.

We found two novel skeleton rearrangement reactions. The one was the reaction from coumarin derivatives having an electron-withdrawing group at the 3-position with dimethylsulfoxonium methylide to cyclopenta[b]benzofuran derivatives. The other was the reaction from benzo[b]cyclobuta[d]pyran derivatives having an electron-withdrawing group at the 2a-position to tetrahydrodibenzofuran derivatives. Interestingly, the latter reaction proceeded stereoconvergently regardless of the stereochemistry at the 1-position in the cyclobutane compounds. Driving forces of these reactions would be attributable to release of the ring strain including in a cyclopropane ring and cyclobutane ring. These methodologies were applied to the total synthesis of linderol A, which is a constituent of Lindera umbellata (Lauraceae) and has a potent inhibitory activity on melanin biosynthesis, and the synthesis was performed in 14 steps, 34% overall yield. Furthermore, the uncertain absolute structure of linderol A was determined, and its asymmetric synthesis was also achieved.

Eleven 3-substituted isocoumarins and a benzylidenephthalide were synthesized through thermal cyclization reaction of delta- and gamma-ketoamides, respectively. Subsequent deprotection of the hydroxyl groups of the resulting isocoumarin and benzylidenephthalide compounds afforded thunberginols A, B, and F, respectively, which originated from the processed leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO. The synthesized isocoumarins and thunberginols were evaluated for their anti-allergic activity, in which thunberginol B exhibited the highest inhibitory potency on the degranulation of RBL-2H3 cells induced by antigen. Structure-activity relationship studies were carried out to determine the necessary substituents on the 3-phenylisocoumarin skeleton for inhibitory activity.

The first asymmetric total synthesis of (-)-Linderol A, a potent inhibitor of melanin biosynthesis of cultured B-16 melanoma cells, has been achieved via two key reactions: a diastereoselective [2+2] photocycloaddition of a coumarin-3-carboxylate bearing a chiral auxiliary with 3-methyl-1-butene and a subsequent stereoconvergent transformation of the photoadducts with use of dimethylsulfoxonium methylide to afford a tetrahydrodibenzofuran derivative.

We report the details of the first total synthesis of erythromycin B using two different strategies for the end game. The first of these follows a classical approach in which the desosamine and cladinose residues are sequentially appended to a macrocyclic lactone, which was formed by cyclization of a seco acid derivative, to give a bis-glycosylated macrolide intermediate that is converted into erythromycin B. The second strategy features an abiotic approach in which a seco acid bearing a desosamine residue is cyclized to give a monoglycosylated macrocyclic lactone that is then transformed into erythromycin B via a sequence of steps involving refunctionalizations and a glycosylation to introduce the cladinose moiety. Attempts to prepare a bis-glycosylated seco acid by de novo synthesis were unsuccessful. The syntheses of the key seco acid intermediates feature the oxidative transformation of a furan containing C(3)–C(10) to provide a dioxabicyclo[3.3.1]nonenone that served as a template on which to create the stereocenters at C(6) and C(8). A stereoselective aldol reaction was used to establish the C(11)–C(15) segment, and a stereoselective crotylation was implemented to introduce the propionate subunit comprising C(1)–C(2).

種子の乾熱処理および火炎放射処理が帰化アサガオ類（ホシアサガオ（Ipomoea triloba），マメアサガオ（I. lacunosa），マルバアサガオ（I. purpurea），マルバアメリカアサガオ（I. hederacea var. integriuscula）およびマルバルコウ（I. coccinea））の発芽に及ぼす影響と，火炎放射後の湛水が種子の生存に及ぼす影響について調査した。80°Cで30分間乾熱処理した場合，5草種の発芽率（吸水，膨潤した種子の割合）は21.1∼97.8％であった。マメアサガオ（21.1%）とマルバアサガオ（47.8%）を除く3草種は，72.2∼97.8％と高い発芽率を示した。一方，火炎放射処理を3秒間行った場合，発芽率は94.4∼100.0%と5草種ともほぼ完全に発芽した。さらに火炎放射処理後の種子は湛水条件下に2ヶ月間埋土されることにより，5草種全てにおいて100%死滅することがわかった。本研究より帰化アサガオ類の防除において，種子散布後に圃場地表面を火炎放射処理し，その後湛水することが有効であることが示唆された。

Pyrrolophenanthridinone derivatives including the natural products were readily synthesized by samarium(II)-mediated reductive cyclization of aryl radical onto a benzene ring under mild reaction conditions. This methodology was applied to the concise synthesis of anhydrolycorinone, a natural pyrrolophenanthridinone and a precursor of hippadine and anhydrolycorine.

The majority of hematopoietic stem cells (HSCs) are maintained in a quiescent state to minimize premature exhaustion induced by various stresses. However, quiescent HSCs are vulnerable to mutagenesis because of attenuated DNA repair and DNA damage response programs. Basal abundant expression of prosurvival BCL-2 proteins further endows HSCs with high resistance to apoptosis. In contrast, HSCs elicit strong activation of p53 upon DNA damage, resulting in enhanced activation of proapoptotic BCL-2 signals through p53. ASPP1, an apoptosis-stimulating protein of p53, is highly expressed in HSCs and preserves HSC pool integrity via selective induction of apoptosis. In this paper, we discuss the role of p53 and mitochondrial apoptosis in HSC regulation and introduce the current understanding of how p53 activity is regulated to achieve a good balance between maintaining the HSC pool and preventing hematological malignancies.

Reuse of chiral ruthenium catalyst in catalytic asymmetric transfer hydrogenation (CATH) has attracted attention from economic and environmental viewpoints, and reactions using ionic liquids (ILs) as solvent are recognized as one of the most useful methods for reuse of the catalyst. We synthesized (1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (TsDPEN) derivatives with various ionic moieties, and investigated the effect of their structure with respect to catalytic ability and recyclability in CATH with ILs. Ligand 3a having an imidazolium group showed the best results, and significant differences were observed depending on the structure of the ionic moiety or the length of the alkyl chain connecting the ligand site and the ionic moiety. Among various prochiral ketones used as substrates at various cycles, 3a showed a relatively good result.

A novel method for indole skeleton synthesis under mild conditions mediated by samarium(II) diiodide has been developed. The reaction of N-allenyl-2-iodoaniline derivatives with SmI2 in the presence of HMPA and i-PrOH at 0 °C afforded indole derivatives in high yields.

Endophytic fungi belonging to the genus Neotyphodium that form mutualistic associations with grasses of the subfamily Pooideae are ecologically and agriculturally important, producing mycotoxins that affect grazing animals and some insect pests. After our first report of naturalized Italian ryegrasses (Lolium multiflorum, annual ryegrass) infected with a Neotyphodium endophyte in Japan, the identity of this endophyte, the nature of its association with host grasses and its distribution, as well as the possible presence of toxic alkaloids have been of interest. To answer these questions we conducted surveys covering the western part of Japan to determine the distribution of infected Italian ryegrasses. Further, to identify the endophyte we used microscopy to determine its distribution in infected grasses and we applied DNA analysis using the ribosomal RNA gene (rDNA) to compare strains of this endophyte obtained from different geographic locations. Finally, we examined seed obtained from endophyte-infected Italian ryegrasses using high-performance liquid chromatograph (HPLC) and gas chromatograph. These studies indicated that naturalized Italian ryegrass in all three islands surveyed; Honshu, Kyushu and Shikoku, was frequently infected with N. occultans. N-formyl loline, an insect toxin, and peramine, a feeding deterrent were detected in the infected seed samples, but neither ergovaline nor lolitrem B (causal agents of grazing animal toxicity) were detected. These chemical analyses indicated that N. occultans infection of Italian ryegrasses may provide some influence on the insect fauna of the area through the chemicals active against insects, but was unlikely to be toxic to grazing animals.

A novel oxazine ring formation method was established using the reaction of 2-acetyl-( E )-3-styrylcarbonylaminobenzo[ b ]furans ( 4 ) with Vilsmeier–Haack–Arnold reagent to afford ( E and Z )-(( E )-2-styrylbenzo[ b ]furo[3,2- d ][1,3]oxazin-4-ylideno)acetaldehydes ( 5 ). ( Z )-4-(8-Bromo-( E )-2-styrylbenzo[ b ]furo[3,2- d ][1,3]oxazin-4-ylideno)but-( E )-2-enoic acid ethyl ester ( 6b ), derived from ( Z )- 5a , showed significantly potent anti-osteoclastic bone resorption activity comparable to 17 β -estradiol (E 2 ).

Homonuclear Diels–Alder dimerization of various 5-ethenyl-2-phenylsulfanyl-1H-imidazoles provided a novel highly regio- and stereoselective route to the preparation of multifunctionalized 4,5,6,7-tetrahydrobenzimidazoles, which is the basic skeleton of ageliferin, a biologically active pyrrole-imidazole marine alkaloid. The reaction was applied to the synthesis of 12,12′-dimethylageliferin.

Ca(2+) release from intracellular Ca(2+) stores, a pivotal event in Ca(2+) signaling, is a 'quantal' process; it terminates after a rapid release of a fraction of stored Ca(2+). To explain the 'quantal' nature, 'all-or-none' model and 'steady-state' model were proposed. This article shortly reviews these hypotheses and considers a recently proposed mechanism, 'luminal potential' model, in which the membrane potential of Ca(2+) store regulates Ca(2+) efflux. By reassessing the 'quantal' nature, other important features of Ca(2+) signaling, oscillation and synchronization, are highlighted. The mechanism for 'quantal' Ca(2+) release may underlie the temporal and spatial control of Ca(2+) signaling.

Asymmetric synthesis of a novel non-benzodiazepine hypnotic drug Ramelteon (TAK-375) was accomplished via asymmetric hydrogenation. Development of the substrate design revealed that a novel class of substrate, allylic acylamine 4a, was hydrogenated with a Ru-BINAP catalyst in 95% ee and 98% yield. The effectiveness and robustness of the reaction were demonstrated on a 700-g scale.

Dopamine modulates synaptic transmission in various brain regions. The disorder of dopamine system may be related to neurodevelopmental dysfunction. However, the action of dopamine on synaptic transmission during development is largely unknown. We studied the effect of dopamine on GABAergic and glutamatergic transmission in neonatal rat hippocampus from the early period of synapse formation by whole-cell patch-clamp recordings from CA1 pyramidal cells. Dopamine (100 muM) profoundly decreased the amplitude of GABA(A) receptor-mediated postsynaptic currents (GABA(A)-PSCs) to 32.2+/-5.4% (mean+/-S.E.M., EC(50): 2.9 muM) in the first postnatal week, when GABA provides excitatory drive. Dopamine also decreased the amplitude of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) to 29.1+/-2.7% (EC(50): 18.7 muM) in the second postnatal week, when glutamate responses first appear. The dopamine-induced inhibition declined after these periods and became only partial after postnatal day 30. Further we identified the receptor subtype involved in the dopamine-induced inhibition as phosphatidylinositol-linked D1-like receptor, since 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol hydrobromide (SKF 83959), a selective agonist for phosphatidylinositol-linked D1-like receptor, clearly mimicked the action of dopamine, and 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), an inhibitor of phospholipase C, significantly reduced the dopamine-induced inhibition. Dopamine did not change the response to puff-applied GABA or kainic acid, nor the amplitude of miniature GABA(A)-PSCs or miniature EPSCs. These results suggest that the activation of phosphatidylinositol-linked D1-like receptor profoundly suppresses the excitatory transmission during the early period of synapse formation in the developing hippocampus by presynaptic mechanisms. This study firstly demonstrates the effect of phosphatidylinositol-linked D1-like receptor on synaptic transmission.

Reaction of 1-substituted 3-alkenyl-1 H -indoles with an equimolar amount of trifluoroacetic acid in dichloromethane gave cyclic dimers, 1,3- trans - N , N ′-disubstituted cyclopent[ b ]indoles, in 53–84% yields as sole products through an acid-mediated stereoselective cyclo -dimerization process. The structure of the cyclic dimer derived from 3-cyclopentylidenemethyl-1-methyl-1 H -indole was elucidated by X-ray crystallographic analysis.

In the male newt Cynops pyrrhogaster, prolactin (PRL) acts directly on the central nervous system and induces courtship behavior. As a step to elucidate the localization of neurons on which PRL acts, we developed a polyclonal antibody against an oligopeptide having a sequence completely identical with a part of the sequence of PRL receptors (PRLRs) of two species of newts, C. pyrrhogaster and C. ensicauda, and performed an immunohistochemical study with this antibody. PRLR-immunoreactive cells were observed in the medial amygdala, anterior preoptic area, magnocellular preoptic nucleus, suprachiasmatic nucleus, nucleus of the periventricular organ, ventral hypothalamic nucleus, and choroid plexus. We also performed in situ hybridization with a (35)S-labeled newt PRLR antisense RNA probe and detected signals in the preoptic area and choroid plexus. Colocalization of both PRLR-like immunoreactivity and arginine vasotocin-like or mesotocin-like immunoreactivity was demonstrated in the magnocellular preoptic nucleus. This is the first report of PRLR localization in the amphibian brain.

The effects of intracerebroventricular (ICV) and intraperitoneal (IP) injections of ovine prolactin (PRL), antiserum against newt PRL, and antibody against the newt PRL receptor on the expression of courtship behavior of male newts, Cynops pyrrhogaster, were studied to see whether PRL acts centrally or peripherally to induce the behavior. Injections of PRL by either route into gonadotropin-primed males enhanced the expression of the behavior dose-dependently. The minimum effective amount of ovine PRL administered intracerebroventricularly was 0.1 microg, whereas it was 100 microg when injected intraperitoneally. ICV injection of antiserum against newt PRL blocked the spontaneously occurring male courtship behavior when the anti-newt PRL serum was given either intracerebroventricularly or intraperitoneally. The minimum effective dose of the antiserum administered intracerebroventricularly was 0.05 microl, whereas it was 20 microl when injected intraperitoneally. Neither ICV nor IP injection of preimmune serum affected the expression of the behavior. Furthermore, ICV, but not IP, administration of 0.3 microg of anti-newt PRL receptor antibody, purified from antiserum against newt PRL receptor by use of an antigen-conjugated affinity column, blocked the spontaneously occurring courtship behavior in sexually developed males. Neither ICV nor IP injection of the same amount of normal rabbit IgG affected the expression of the behavior. The results strongly suggest that endogenous PRL enhances the behavior by acting centrally through the PRL receptors localized in the brain area.

Reaction of 1- tert -butoxycarbonyl-3-cyclopentylidenemethyl-1 H -indole with an excess of trifluoroacetic acid in dichloromethane at room temperature gave a cyclic dimer, 13-cyclopentyl-6,7,12,13-tetrahydrospiro[5 H -cyclohepta[1,2- b :4,5- b ′]diindole-6,1′-cyclopentane] in 73% yield as the sole product through a novel cyclo-dimerization process. Structure of the cyclic dimer derived from 5-bromo-1- t -butoxycarbonyl-3-cyclopentylidenemethyl-1 H -indole was elucidated by X-ray crystallographic analysis.

To clarify whether the unique postural control of the upside-down swimming catfish (Synodontis nigriventris, family Mochokidae) is related to the histological characteristics of the otolith organs, we performed light microscopic observation of the utricle, the saccule and the lagena. The histological aspects of the otolith organs were compared between S. nigriventris and Synodontis multipunctatus, which belong to the same genus. S. multipunctatus usually shows upside-up swimming posture except for feeding behaviour near water surface. As controls, we additionally used a miniature catfish, Corydoras paleatus and goldfish, Carassius auratus, which shows upside-up swimming posture. We concluded that the structural aspects of the otolith organs did not cause the unique postural control of S. nigriventris. Light microscopic observation clarified the following aspects: (1) The utricle of S. nigriventris was located at the anterior region of the otocyst and under the semicircular canals, and the saccule and the lagena were located at the posteroventral region of the otocyst like those of S. multipunctatus and the other two fishes. (2) The hair cells of the utricle were arranged on the horizontal plane of the fishes with a variation in cell size at the ventral and ventrolateral sites in S. nigriventris, S. multipunctatus and the other two fishes. (3) The hair cells of the saccule and lagena of S. nigriventris, S. multipunctatus and C. auratus presented perpendicular to the horizontal plane of the fish. (4) Region-specific differences in the size and shape of the hair cells of S. nigriventris were observed along the three-dimensional axes of the otolith organs like those of S. multipunctatus and the other two fishes. It is unlikely that the unique postural control of upside-down catfish is related to the localization of the utricle, the saccule and the lagena and the distribution of the different types of hair cell of the otolith organs. Furthermore, the distribution of the hair cells suggests that the otolith organs in S. nigriventris can detect three-dimensional postural changes like the organs of other fishes showing generally observed upside-up swimming posture.

1,2a-Disubstituted benzo[b]cyclobuta[d]pyrans, which were prepared by photochemical [2+2] cycloaddition between coumarins and alkenes, were treated with two equivalents of dimethyl-sulfoxonium methylide. 1,3-Disubstitutedtetrahydrodibenzofurans having r-1,t-4a,t-9b stereochemistry were obtained stereoconver-gently regardless of the stereochemistry of the 1-position in the cyclobutane derivatives. This methodology was applied to the second-generation synthesis of (′)-linderol A, a melanin biosynthesis inhibitory active natural product.

Neotyphodium endophytes are vertically transmitted fungal symbionts of grasses. Being pest-repelling and growth-promoting agents for their hosts, and also potential mycotoxin producers, their detection in plants is important. Observation of chemically cleared flowers of infected grasses (Festuca arundinacea, F. pratensis, Lolium perenne, and L. multiflorum) using differential interference contrast microscopy revealed the existence of endophytes within immature ovaries of host plants. This observation method provides an accurate and easy way to detect and distinguish Neotyphodium endophytes in flowering host grasses and to investigate the seed transmission process, which is critical to their life cycle, and the practical use of infected plants.

Reaction of 2-(1-chloro-2,2-dimethylpropyl)-1-methyl-1H-irnidazoles with diethyl methylmalonate in the presence of NaH gave a normal SN product, 2-[(1,1-diethoxycarbonylethyl)-2,2-dimethylpropyl]-1-methyl-1H-imidazole (2a), and two tele-reaction products, 5-(1,1-diethoxycarbonylethyl)-1-methyl-2-(2,2-dimethylpropyl)-1H-imidazole (3a) and trans-4,5-di-(1,1-diethoxycarbonylethyl)-4,5-dihydro-1-methyl-2-(2,2-dimethylpropyl)-1H-imidazole (4a) in 5, 17 and 70% yields, respectively. The scope and mechanism of this reaction are discussed.

On tunnel excavation, a prediction of geological conditions ahead of face is of the utmost importance to keep rapid driving and safety works. Fukui et al. in 2004 investigated the drilling performance at Suzuka tunnel with special care to the effect of hole length up to 50 m, and proposed V* (normalized penetration rate) to estimate rock mass properties ahead of face. In this study, the method proposed by Fukui et al. was fully discussed and slightly modified. Thereafter, the method was applied to estimate rock mass properties at Suzuka tunnel and systematic in-situ measurements of V* were carried out through the tunnel. It was found that the reciprocal of V* is a good indicator for rock mass properties and suits the in-situ usage. The reciprocal of V* has strong correlation with rock mass strength estimated by TBM cutting force and very useful to estimate and predict the rock mass properties ahead of face. For example, a fracture zone can be predicted by an abrupt change of the magnitude.

Novel 3-acetoacetylaminobenzo[b]furan derivatives having a modified triene system at the 3-position were synthesized starting with 3-aminobenzo[b]furans. The enol isomers, 3-[(3-hydroxybut-2-enonyl)amino]benzo[b]furans (), of the 3-acetoacetylaminobenzo[b]furans were obtained as stable isomers owing to formation of a hydrogen bonding between the enol hydroxyl group and the amidocarbonyl group. The planarity of the C-2 substituent through the C-3 side chain suggested the existence of a modified conjugational triene system in the enol compound. Cysteinyl leukotriene 1 and 2 receptor antagonistic activities for these compounds were evaluated. 2-(4-Cyanobenzoyl or ethoxycarbonyl)-3-[(2-cyano-3-hydroxybut-2-enonyl)amino]benzo[b]furans (, ) were moderately active.

In this study, systematic in-situ tests along Suzuka tunnel were carried out to examine the drilling performance in case of drilling holes up to 50 m depth. Special care was taken to clarify the effect of hole length on drilling performance such as penetration rate, rotational torque and oil pressure applied to the rock drill.Results can be summarized as follows;1) Averaged penetration rate has a declining trend with increase of hole length. Energy of elastic wave is gradually decreasing while propagating rods. Averaged decrease of penetration rate was 1.5% per 3 m-length rod.2) Averaged penetration rate fluctuated especially at 20m and 40m of hole length. It was considered that an interaction between piston movement and reflected wave from the bit caused this considerable amount of fluctuation.3) Rotational torque has an increasing trend with increase in hole length and frictional resistance between drill rod and hole.

Intracellular Ca(2+) is a regulatory signal for cell proliferation. To reveal Ca(2+) signal dynamics during cell cycle, we applied Ca(2+) fluorescence imaging to the neural retina of chick embryo, where the soma changes its position during the cell cycle. Purinoceptors were stimulated to cause Ca(2+) release from Ca(2+) stores, since the purinoceptor activation promotes DNA synthesis. Ca(2+) rises occurred in the nucleoplasm of cells at around S-phase. The soma of S-phase cell is located in the inner layer of the retinal neuroepithelium and issues an outer process, which extends to the ventricular surface. Fluorescent probes for endoplasmic reticulum (ER) showed that the ERs in the outer process and the nuclear envelope (NE) or peri-nuclear ER formed the Ca(2+) store. Depletion of the Ca(2+) store induced capacitative Ca(2+) entry (CCE), which caused Ca(2+) rises in the terminal of outer process and soma. The store-operated Ca(2+) signaling declined in M-phase cells and postmitotic cells (retinal ganglion cells (RGCs)) with the loss of the outer process. These results suggest that the Ca(2+) signaling to nucleus via the store-operated system including the ERs in the outer process is crucial for the cell cycle progression in the retinal neuroepithelium.

We synthesized a novel series of benzocycloalkene derivatives and evaluated their binding affinities to melatonin receptors. To control the spatial position of the amide group, one of the important pharmacophores, we incorporated an endo double bond, an exo double bond (E- and Z-configurations), and a chiral center (R- and S-configurations) at position 1. The indan derivatives with the S-configuration at position 1 were the most promising in terms of potency and selectivity for the human melatonin receptor (MT(1) site), while compounds with the R-configuration showed little potential. Our next attempt was to investigate the most favorable conformation of the methoxy group, the other important pharmacophore for binding to the MT(1) receptor. The introduction of a methyl group at position 5 of the indene ring conserved affinity; however, at position 7, it caused a decrease in affinity. These results suggested that the substitution at position 7 forced the methoxy group to adopt an unfavorable orientation. The optimization of the condensed ring size and substituents led to (S)-8d [(S)-N-[2-(2,3-dihydro-6-methoxy-1H-inden-1-yl)ethyl]propionamide], which had high affinity for the human MT(1) receptor (K(i) = 0.041 nM) but no significant affinity for the hamster MT(3)receptor (K(i) = 3570 nM). In addition, a practical synthetic method of chiral N-[2-(2,3-dihydro-1H-inden-1-yl)ethyl]alkanamides employing asymmetric hydrogenation with (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru has been established.

Diels–Alder-type dimerization of various 5-ethenyl-2-phenylsulfanyl-1 H -imidazoles provided a novel highly regio- and stereoselective route to the preparation of multifunctionalized 4,5,6,7-tetrahydrobenzimidazoles, the basic skeleton of ageliferin, a biologically active pyrrole–imidazole marine alkaloid. The reaction was applied to the synthesis of 12,12′-dimethylageliferin.

The first total synthesis of naamine C and pyronaamidine, highly substituted and cytotoxic imidazole marine alkaloids of a certain kind of sponge, was achieved through an eight-step reaction starting from 1-methyl-2-phenylthio-1H-imidazole.