Water modulates the lamellar structure and interlayer correlation of poly(perfluorooctyl acrylate) films: a specular and off-specular neutron scattering study

Comb-like polymers with pendant-like perfluorocarbon side chains self-assemble into smectic lamellae and have been extensively used as water-repellent, hydrophobic coating materials characterized by large water contact angles (θ > 120°). As poly(perfluorooctyl acrylate) films are “apparently hydrophobic” (θ > 120°), the interaction of such materials and water molecules has been largely overlooked. To unravel the molecular-level interactions between water and apparently hydrophobic polymers, specular and off-specular neutron scattering experiments were conducted at defined osmotic pressure ΠH2O. The poly{2-[(perfluorooctylethyl)carbamate]ethyl} acrylate (PFAUr-C₈), which had a carbamate linker, transitioned to another lamellar phase at 89 °C. At T = 25 °C; the lamellar periodicity of PFAUr-C₈ slightly increased with decreasing osmotic pressure, while the vertical correlation length increased. However, the poly[(perfluorooctyl)ethyl] acrylate (PFA-C₈) that did not contain a carbamate linker directly transitioned to a disordered phase at 84 °C. The lamellar periodicity of PFA-C₈ was largely independent of the osmotic pressure, suggesting that PFA-C₈ was poorly hydrated. Remarkably, the vertical correlation length decreased with decreasing osmotic pressure. Because hydration facilitated by the linker modulated the smectic lamellae of the poly(perfluoroalkyl acrylate), water molecules could be used to optimize the self-assembly of apparently hydrophobic liquid crystalline polymers

ISR-DEPENDENT METABOLIC REGULATION

The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation‐dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand‐activated skeletal muscle–specific derivative of the eIF2α protein kinase R‐like ER kinase revealed the expected up‐regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small‐molecule ISR activator that promoted Fgf21 expression in cell‐based screens and by implication of the ISR‐inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell‐autonomous proteostasis and amino acid metabolism, but also affects non‐cell‐autonomous metabolic regulation by induced expression of a potent myokine.—Miyake, M., Nomura, A., Ogura, A., Takehana, K., Kitahara, Y., Takahara, K., Tsugawa, K., Miyamoto, C., Miura, N., Sato, R., Kurahashi, K., Harding, H. P., Oyadomari, M., Ron, D., Oyadomari, S. Skeletal muscle‐specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21‐mediated non‐cell‐autonomous energy metabolism

Control cell migration by engineering integrin ligand assembly

Advances in mechanistic understanding of integrin-mediated adhesion highlight the importance of precise control of ligand presentation in directing cell migration. Top-down nanopatterning limited the spatial presentation to sub-micron placing restrictions on both fundamental study and biomedical applications. To break the constraint, here we propose a bottom-up nanofabrication strategy to enhance the spatial resolution to the molecular level using simple formulation that is applicable as treatment agent. Via self-assembly and co-assembly, precise control of ligand presentation is succeeded by varying the proportions of assembling ligand and nonfunctional peptide. Assembled nanofilaments fulfill multi-functions exerting enhancement to suppression effect on cell migration with tunable amplitudes. Self-assembled nanofilaments possessing by far the highest ligand density prevent integrin/actin disassembly at cell rear, which expands the perspective of ligand-density-dependent-modulation, revealing valuable inputs to therapeutic innovations in tumor metastasis

Skeletal muscle–specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21–mediated non–cell-autonomous energy metabolism

The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation-dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand-activated skeletal muscle-specific derivative of the eIF2α protein kinase R-like ER kinase revealed the expected up-regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small-molecule ISR activator that promoted Fgf21 expression in cell-based screens and by implication of the ISR-inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine.Ministry of Education, Culture, Sports, Science and Culture (MEXT) of Japan Inoue Foundation for Science Mitsubishi Foundation Uehara Memorial Foundation Naito Foundation Cell Science Research Foundation Takeda Science Foundation Sankyo Foundation Ono Medical Research Foundation Mochida Memorial Foundation Ube Foundation Kowa Life Science Foundation Suzuken Memorial Foundation Kanae Foundation Japan Diabetes Foundation Japan Society for Promotion of Science (JSPS) EU FP7. Grant Number: 277713 Wellcome Trust. Grant Number: 084812/Z/08/

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): A study protocol for a multicenter randomized phase III trial

金沢大学附属病院泌尿器科Background: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. Methods/design: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. Discussion: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. Trial registration: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529. Registrated 11/1/2014. © 2017 The Author(s)

Characterization of autonomous Dart1 transposons belonging to the hAT superfamily in rice

An endogenous 0.6-kb rice DNA transposon, nDart1-0, was found as an active nonautonomous element in a mutable virescent line, pyl-v, displaying leaf variegations. Here, we demonstrated that the active autonomous element aDart in pyl-v corresponds to Dart1-27 on chromosome 6 in Nipponbare, which carries no active aDart elements, and that aDart and Dart1-27 are identical in their sequences and chromosomal locations, indicating that Dart1-27 is epigenetically silenced in Nipponbare. The identification of aDart in pyl-v was first performed by map-based cloning and by detection of the accumulated transposase transcripts. Subsequently, various transposition activities of the cloned Dart1-27 element from Nipponbare were demonstrated in Arabidopsis. Dart1-27 in Arabidopsis was able to excise nDart1-0 and Dart1-27 from cloned sites, generating footprints, and to integrate into new sites, generating 8-bp target site duplications. In addition to Dart1-27, Nipponbare contains 37 putative autonomous Dart1 elements because their putative transposase genes carry no apparent nonsense or frameshift mutations. Of these, at least four elements were shown to become active aDart elements in transgenic Arabidopsis plants, even though considerable sequence divergence arose among their transposases. Thus, these four Dart1 elements and Dart1-27 in Nipponbare must be potential autonomous elements silenced epigenetically. The regulatory and evolutionary implications of the autonomous Dart1 elements and the development of an efficient transposon-tagging system in rice are discussed

ハンカイ シンケイ ドウテイ ニ NIMシステム オ モチイタ Zenkerケイシツ ノ 1レイ

　Zenker憩室はKillian’s間隙に発生した憩室であり，全消化管憩室の0.1%の頻度と稀である．今回われわれは，術中神経モニタリングシステムであるNIMシステム(NERVE INTEGRITY MONITORING SYSTEM；以下，NIMと略記)をZenker憩室の手術で使用し，反回神経を容易に同定することが可能であったので報告する．　症例は67歳，女性．数年前から咽頭部の違和感を自覚し，２カ月前から増悪したため当院外来を受診した．精査の結果，症状を認めるZenker憩室と診断し，手術を施行した．NIMを使用して反回神経の走行を確認しつつ憩室を同定した．憩室を切除後，二層縫合(Albert-Lembert吻合)して閉鎖した．術中内視鏡検査を施行し，食道に狭窄や漏れがないことを確認した．輪状咽頭筋切開を追加し，甲状腺を縫合部の前面で固定して縫合部を補強した．ドレーンを留置して手術を終了した．術後経過は良好で手術から14日目に退院とし，退院後１ヶ月の時点で症状は改善していることを確認した．　Zenker憩室の手術で反回神経損傷は回避すべき合併症のひとつである．甲状腺手術で使用するNIMはZenker憩室の手術においても反回神経の同定に使用することで，神経損傷のリスクを下げる可能性がある．　Zenker’s diverticulum is a diverticulum that develops in the Killian’s gap. The frequency of its occurrence is 0.1% of all digestive tract diverticulum. The present study reports that the NIM system can be useful during Zenker’s diverticulum surgery for easily identifying recurrent laryngeal nerve.　The present case is of a 67-year-old woman. She was aware of discomfort in her pharyngeal region for several years. She had been aggrieved for the past 2 months, and therefore was admitted to our hospital’s outpatient clinic. Following examination, we diagnosed Zenker’s diverticulum and performed surgery. We identified recurrent laryngeal nerve using NIM. We dissected the diverticulum and sutured in layers and closed. Intraoperative endoscopy was performed to confirm that there was no stenosis or leakage in the esophagus. We performed ring pharyngeal muscle incision. We fixed the thyroid gland in front of the suture to reinforce it. There was no untoward event postoperatively, and the patient was discharged from the hospital on day 14 after the surgery. We confirmed that the symptom had improved at 1 month after discharge.　NIM used in thyroid surgery is also useful in identifying the recurrent laryngeal nerve during Zenker’s diverticula surgery and may help reduce the risk of nerve damage