多価不飽和脂肪酸を２位に結合するホスファチジルコリンの炭素アナローグの合成

Carbon analogues of Phosphatidylcholines having linoleic or arachidonic acid at the 2-position were synthesized. The synthetic route involves conversion of the polyunsaturated fatty acid iodination. The derivatives were converted to diols by LiAIH4 reduction and submitted to lipase-catalyzed monostearoylation in isopropylether. The mono-ester was converted to phoshatidylcholines by the usual phosphodiester synthesis.自然界に広く存在するホスフォリパーゼA2はグリセロリン脂質の2位のエステル結合を選択的に切断する酵素であり,消化,アラキドン酸カスケードの起動,リン脂質過酸化物の代謝等,生理作用に広く関わっている。本研究ではホスフォリパーゼA2の基質ミメテイックとしてホスファチジルコリンの2位エステル結合が炭素-炭素結合に置き換わった化合物をアラキドン酸とステアリン酸を出発原料としてリパーゼ触媒によるアシル化反応及び有機化学反応によって合成した

Differential determinants of physical daily activities in frail and nonfrail community-dwelling older adults

AbstractBackground/PurposeThe purpose of this study was to determine whether or not daily activities determined by average daily steps are associated with age, gender, body mass index, fear of falling, and physical functions (locomotive function, balance function, and muscle power) in community-dwelling nonfrail and frail older adults.MethodsThis is a cross-sectional study conducted in community-dwelling older adults in Japan. Based on the Timed Up and Go (TUG) test, 629 elderly adults were divided into two groups: 515 were grouped to nonfrail elderly (TUG time less than 13.5 seconds, mean age 77.0±7.2 years) and 114 to frail elderly (TUG time of 13.5 seconds or more, mean age 76.1±7.5 years). Daily physical activities were determined by average daily steps measured by pedometer and four other physical function tests (10-m walk test, single-leg standing, functional reach, and five-chair stand test) were performed along with the assessment of fear of falling.ResultsStepwise regression analysis revealed that age, gender, 10-m walk test, and single-leg standing were significant and independent determinants of the average step counts in the nonfrail elderly (R2=0.282, p<0.001), whereas fear of falling was the only significant and independent determinant of the average step counts in the frail elderly (R2=0.119, p<0.001).ConclusionThese results indicate that differential factors may be related to daily activities depending on the level of frailty in community-dwelling older adults

Sn-1位に多価不飽和脂肪酸を結合する2-0-methoxyethoxymethylglycerolの立体配置決定

A correlation of optical rotation, optical purity and configuration of the asymmetric center was done for 2-0-methoxyethoxymethylglycerol bearing polyunsaturated fatty acyl group at sn-1 position. This compound was enzymatically prepared and is an important starting material for the syntheses of optical active glycerophospholipids naving polyunwaturated fatty acyl groups.自然界に広く存在し，重要な生理機能を担っている多価不飽和脂肪酸結合リン脂質の化学的合成に必要な出発原料としての2-0-methoxyethoxymethylglycerolの立体配置と光学純度を，立体配置・光学純度既知の物質に化学的に誘導し，それらの比旋光度をお互いに比較する事により決定した

Synthesis of 2-amino- and 2-arylazoazulenes via nucleophilic aromatic substitution of 2-chloroazulenes with amines and arylhydrazines

The SNAr reaction of 2-chloroazulene derivative 1 with ethoxycarbonyl groups at the 1,3-positions of the azulene ring with several amines afforded the corresponding 2-aminoazulenes 3-9 in excellent yields. 2-Chloroazulene (2) without the electron-withdrawing groups reacted with highly nucleophilic cyclic amines (i.e., morpholine, piperidine and pyrrolidine) under the high-temperature conditions in a sealed tube to produce the corresponding 2-aminoazulenes 10-12 in good yields. 2-Aminoazulenes 10-14 without the electron-withdrawing groups were also obtained in good yields by the treatment of compounds 3-7 with 100% H3PO4, but in the cases of the reaction of 8 and 9 with a secondary amine function, the decomposition of the products resulted. The synthesis of 2-arylazoazulenes 15-18 was also established via the SNAr reaction of 1 with arylhydrazines. The optical and electrochemical properties of the 2-arylazoazulene derivatives were examined by UV/Vis spectroscopy, theoretical calculations and voltammetric experiments.ArticleORGANIC & BIOMOLECULAR CHEMISTRY. 94(10):3917-3923 (2017)journal articl

A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia

Cofilin mediates lamellipodium extension and polarized cell migration by stimulating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by phosphorylation at Ser-3 and reactivated by cofilin-phosphatase Slingshot-1L (SSH1L). Little is known of signaling mechanisms of cofilin activation and how this activation is spatially regulated. Here, we show that cofilin-phosphatase activity of SSH1L increases ∼10-fold by association with actin filaments, which indicates that actin assembly at the leading edge per se triggers local activation of SSH1L and thereby stimulates cofilin-mediated actin turnover in lamellipodia. We also provide evidence that 14-3-3 proteins inhibit SSH1L activity, dependent on the phosphorylation of Ser-937 and Ser-978 of SSH1L. Stimulation of cells with neuregulin-1β induced Ser-978 dephosphorylation, translocation of SSH1L onto F-actin–rich lamellipodia, and cofilin dephosphorylation. These findings suggest that SSH1L is locally activated by translocation to and association with F-actin in lamellipodia in response to neuregulin-1β and 14-3-3 proteins negatively regulate SSH1L activity by sequestering it in the cytoplasm

顎関節におけるHIF-1αの役割

Objective: Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease characterized by permanent cartilage loss. Articular cartilage is maintained in a low-oxygen environment. The chondrocyte response to hypoxic conditions involves expression of hypoxia inducible factor 1α (HIF-1α), which induces chondrocytes to increase expression of vascular endothelial growth factor (VEGF). Here, we investigated the role of HIF-1α in mechanical load effects on condylar cartilage and subchondral bone in heterozygous HIF-1α-deficient mice (HIF-1α+/-). Design: Mechanical stress was applied to the TMJ of C57BL/6NCr wild-type (WT) and HIF-1α+/- mice with a sliding plate for 10 days. Histological analysis was performed by HE staining, Safranin-O/Fast green staining, and immunostaining specific for articular cartilage homeostasis. Results: HIF-1α+/- mice had thinner cartilage and smaller areas of proteoglycan than WT controls, without and with mechanical stress. Mechanical stress resulted in prominent degenerative changes with increased expression of HIF-1α, VEGF, and the apoptosis factor cleaved Caspase-3 in condylar cartilage. Conclusion: Our results indicate that HIF-1a may be important for articular cartilage homeostasis and protective against articular cartilage degradation in the TMJ under mechanical stress condition, therefore HIF-1α could be an important new therapeutic target in TMJ-OA

Structural dynamics of cereal mitochondrial genomes as revealed by complete nucleotide sequencing of the wheat mitochondrial genome

The application of a new gene-based strategy for sequencing the wheat mitochondrial genome shows its structure to be a 452 528 bp circular molecule, and provides nucleotide-level evidence of intra-molecular recombination. Single, reciprocal and double recombinant products, and the nucleotide sequences of the repeats that mediate their formation have been identified. The genome has 55 genes with exons, including 35 protein-coding, 3 rRNA and 17 tRNA genes. Nucleotide sequences of seven wheat genes have been determined here for the first time. Nine genes have an exon–intron structure. Gene amplification responsible for the production of multicopy mitochondrial genes, in general, is species-specific, suggesting the recent origin of these genes. About 16, 17, 15, 3.0 and 0.2% of wheat mitochondrial DNA (mtDNA) may be of genic (including introns), open reading frame, repetitive sequence, chloroplast and retro-element origin, respectively. The gene order of the wheat mitochondrial gene map shows little synteny to the rice and maize maps, indicative that thorough gene shuffling occurred during speciation. Almost all unique mtDNA sequences of wheat, as compared with rice and maize mtDNAs, are redundant DNA. Features of the gene-based strategy are discussed, and a mechanistic model of mitochondrial gene amplification is proposed

Humanoid Robot With Turnover Prevention and Self-Weight Compensation

Q-bot is the human-sized carriage robot for lifting heavy weight objects of in-house logistics, such as storehouse and convenience store. The main feature of Q-bot is the adhesion mechanism beneath the foot, called the turnover prevention Universal Vacuum Gripper (in short TP UVG) that holds its body for turnover prevention and self-weight compensation. Turnover prevention is one of the key technologies of in-house logistic robot for effective use of it. Self-weight compensation is another clue for the robot to achieve the labor work in narrow space. TP UVG is achieved both functions by adhering to uneven ground. The other function of Q-bot is multiple objects graspability based on two-sized Universal Vacuum Gripper by dual-armed manipulation. Q-bot also has omnidirectional movability based on mecanum wheels. In this research, we will report on the development of Q-bot and experiments to prevent the robot from falling when it grabs a heavy object while attached to the ground. We also report Q-bot demonstrations of Future Convenience-Store Challenge in the World Robot Summit 2018

Oral Clostridium butyricum on mice endometritis through uterine microbiome and metabolic alternations

Endometritis occurs frequently in humans and animals, which can negatively affect fertility and cause preterm parturition syndrome. Orally administered Clostridium butyricum, a butyrate-producing gram-positive anaerobe, exhibits anti-inflammatory effects. However, the precise mechanism by which Clostridium butyricum attenuates endometritis remains unclear. This in vivo study evaluated the anti-inflammatory effects of orally administered Clostridium butyricum on uterine tissues. In addition, we conducted uterine microbiome and lipid metabolome analyses to determine the underlying mechanisms. Female Balb/c mice were divided into the following four groups (n = 5–20): (1) mock group, (2) only operation group (mice only underwent operation to exposed uterine horns from the side), (3) control group (mice underwent the same operation with the operation group + perfusion of lipopolysaccharide solution from uterine horns), and (4) Clostridium butyricum administration group (mice underwent the same operation with the control group + oral Clostridium butyricum administration from days 0 to 9). Clostridium butyricum was administered via oral gavage. On day 10, we investigated protein expression, uterine microbiome, and lipid metabolism in uterine tissues. Consequently, orally administered Clostridium butyricum altered the uterine microbiome and induced proliferation of Lactobacillus and Limosilactobacillus species. The effects can contribute to show the anti-inflammatory effect through the interferon-β upregulation in uterine tissues. Additionally, oral Clostridium butyricum administration resulted in the upregulations of some lipid metabolites, such as ω-3 polyunsaturated fatty acid resolvin D5, in uterine tissues, and resolvin D5 showed anti-inflammatory effects. However, the orally administered Clostridium butyricum induced anti-inflammatory effect was attenuated with the deletion of G protein-coupled receptor 120 and 15-lipooxgenase inhibition. In conclusion, Clostridium butyricum in the gut has anti-inflammatory effects on uterine tissues through alterations in the uterine microbiome and lipid metabolism. This study revealed a gut-uterus axis mechanism and provided insights into the treatment and prophylaxis of endometritis

Development of a Multifunctional Lightweight Membrane with a High Specific Power Generation Capacity

As a lighter power generation system, Japan Aerospace Exploration Agency (JAXA) and Sakase Adtech Corp. are developing a demonstrator component named “Harvesting Energy with Lightweight Integrated Origami Structure” (HELIOS), which is a deployable lightweight membrane structure. HELIOS has solar arrays on its surface and demonstrates the technology which enables higher specific power generation capacity compared to the conventional solar array panels. The membrane also has communication antennas, showing the potency of lightweight membrane’s multifunctionality such as large data transmitting by 5G antennas and high-resolution observation by interferometer antennas. This paper presents the component’s concept and design, and the expected achievements