Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group.

The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical properties to the parent peptide, and an improved resistance to peptidase-mediated degradation was observed compared with the non-end-capped peptide obtained using standard recombinant technology

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora

Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. In a double-blind, randomized, placebo-controlled, parallel-group, multi-center study, healthy subjects were randomly assigned to either an LCMUFA oil (saury oil) or a control oil (olive and tuna oils) group. Sixty subjects were enrolled and administrated each oil for 4 weeks. For the animal study, ApoE−/− mice were fed a Western diet supplemented with 3% of either gadoleic acid (C20:1) or cetoleic acid (C22:1) for 12 weeks. Participants from the LCMUFA group showed improvements in endothelial function and a lower trimethylamine-N-oxide level, which is a predictor of coronary artery disease. C20:1 and C22:1 oils significantly improved atherosclerotic lesions and plasma levels of several inflammatory cytokines, including IL-6 and TNF-α. These beneficial effects were consistent with an improvement in the gut microbiota environment, as evident from the decreased ratio of Firmicutes and/ or Bacteroidetes, increase in the abundance of Akkermansia, and upregulation of short-chain fatty acid (SCFA)-induced glucagon-like peptide-1 (GLP-1) expression and serum GLP-1 level. These data suggest that LCMUFAs alter the microbiota environment that stimulate the production of SCFAs, resulting in the induction of GLP-1 secretion. Fish oil-derived long-chain monounsaturated fatty acids might thus help to protect against cardiovascular disease

小学生がうま味の相乗効果を学ぶための味覚授業の実施

The purpose of this study was to assess whether elementary school children were able to learn the synergistic effects of umami flavor through the implementation of a sense of taste class for them. The sense of taste class held for 182 elementary school children (aged, 10–11 years old in Kyoto city). The subjects assessed three types of broths: dried bonito (DB), kombu kelp (KK), and dried bonito-kombu kelp (DB-KK). The subject evaluated the broth for several factors: tastiness, umami flavor, aroma, fishy smell. In addition, children were asked to write their own comments about what they had learned or noticed. A total of 147 healthy subjects were analyzed.The results of the sensory evaluation showed that the children sensed umami flavor and tastiness more significantly in DB-KK broth than in KK broth. They also evaluated the DB broth and DB-KK broth to have a significantly better aroma than KK broth (both at p<0.05). The analysis of the comment showed that 11 children (7.5%) wrote about their understanding of the fundamental taste umami, and 31 children (21.1%) wrote about understanding the synergistic effect of umami flavor. These results suggest that the implementation of the sense of taste class is effective to learn the synergistic effects of umami flavor.論

Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95

Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found that blocking synaptic activity rapidly induces PSD-95 palmitoylation and mediates synaptic clustering of PSD-95 and associated AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic density to transduce this effect. These data demonstrate that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.

Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells

コガタ クライオサンプラー ヲ モチイタ ショウワキチ デノ セイソウケン タイキ サイシュ ジッケン ダイ49ジタイ ジッケン ホウコク

第49次南極地域観測隊(第49次隊)夏期間に昭和基地において,新たに開発した小型クライオサンプラーを用いた成層圏大気採取実験を実施した.小型クライオサンプラーは高圧ネオンガスを断熱膨張させて液体ネオンを製造し,希薄な成層圏大気を固化・液化採取するものであり,既存の大型サンプラーが必要とした液体ヘリウムが不要であること,小型軽量であるために満膨張時容積1000-2000 m3の小型プラスチック気球を用いて成層圏まで飛揚させることが可能であるという特徴がある.2007年12月30日と2008年1月4日に計4機の小型サンプラーを放球し,すべて回収に成功した.そのうち,2機は高度18 km及び25kmの成層圏大気の採取に成功した.採取された大気試料は国内に持ち帰られた後,各種温室効果気体濃度と同位体比の分析が行われた.As a part of summer observations of the 49th Japanese Antarctic Research Expedition, stratospheric whole air sampling experiments were conducted at Syowa Station using newly developed compact cryogenic air samplers. The compact sampler uses liquefied neon (produced in-situ) as a refrigerant to solidify or liquefy atmospheric constituents. Because of its reduced size and weight, the sampler can be launched using small-size balloons (1000&#8211;2000 m3 in volume). On December 30, 2007 and January 4, 2008, a total of 4 samplers were launched from Syowa Station and recovered on the same day as their launches. Two of them functioned as designed and collected stratospheric air samples at altitudes of 18 and 25 km. The air samples were analyzed for greenhouse gas concentrations and stable isotopes after return to Japan