Optimal isotope labelling for NMR protein structure determinations

Nuclear-magnetic-resonance spectroscopy can determine the three-dimensional structure of proteins in solution. However, its potential has been limited by the difficulty of interpreting NMR spectra in the presence of broadened and overlapping resonance lines and low signal-to-noise ratios. Here we present stereo-array isotope labelling (SAIL), a technique that can overcome many of these problems by applying a complete stereospecific and regiospecific pattern of stable isotopes that is optimal with regard to the quality and information content of the resulting NMR spectra. SAIL uses exclusively chemically and enzymatically synthesized amino acids for cell-free protein expression. We demonstrate for the 17-kDa protein calmodulin and the 41-kDa maltodextrin-binding protein that SAIL offers sharpened lines, spectral simplification without loss of information, and the ability to rapidly collect the structural restraints required to solve a high-quality solution structure for proteins twice as large as commonly solved by NMR. It thus makes a large class of proteins newly accessible to detailed solution structure determination.     

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.     

基于建筑类型学的南京中华门门西地区传统民居平面空间演变

以中国古都"城市组织"为研究背景,以古都南京中华门门西历史街区为考察对象,用"建筑类型学"的分析方法对传统民居进行分析,旨在为今后传统民居的保护、传承和利用提供依据.     

SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion

Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9. In adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. By deleting Ccr1 in the background of the cis-Apc/Smad4 mutant, we further show that lack of CCR1 prevents accumulation of CD34(+) iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of transforming growth factor-beta family signaling in tumor epithelium causes accumulation of iMCs that promote tumor invasion.     

Understanding paternal genome demethylation through live-cell imaging and siRNA

Identification of a DNA demethylase responsible for zygotic paternal DNA demethylation has been one of the most challenging goals in the field of epigenetics. Several candidate molecules have been proposed, but their involvement in the demethylation remains controversial, partly due to the difficulty of preparing a sufficient quantity of materials for biochemical analysis. In this review, we utilize a recently developed method for live-cell imaging of mouse zygotes combined with RNA interference (RNAi) to search for factors that affect zygotic paternal DNA demethylation. The combined use of various fluorescent probes and RNAi is a useful approach for the study of not only DNA demethylation but also the spatiotemporal dynamics of histone depositions in zygotes, although it is not appropriate for large-scale screening or knockdown of genes that are abundantly expressed before fertilization. This new technique enables us to understand the epigenetic hierarchy during cellular response and differentiation in preimplantation embryos.     

Stereoselective Total Synthesis of Mycalamides

Mycalamides A （1a） and B （1b） are potent antiviral compounds from a New Zealand sponge of the genus Mycale. Apart from their antitumor property, mycalamide A （1a） exhibits immunosuppressive action by blocking T-cell activation in mice and is significantly more potent than FK-506 and cyclosporine A. Because of their intriguing biological activity, unique structures and scarce supply of these natural products, mycalamides A （1a） and B （1b） have attracted considerable attention as target molecules for total synthesis, and total, formal, or partial syntheses of this family of compounds have been reported.     

Implementation of 3-Valued Paraconsistent Logic Programming Towards Decision Making System of Agents

Due to the rapid development of applications of artificial intelligence and robotics in recent years, the necessity of reasoning and decision making with uncertain and inaccurate information is increasing. Since robots in the real world are always exposed to behavioral inaccuracies and uncertainty arising from recognition methods, they may occasionally encounter contradictory facts during reasoning on action decision.Paraconsistent logic programming is promising to make appropriate action decisions even when an agent is exposed to such uncertain information or contradictory facts, but there has been no implementation of this programming to the best of our knowledge. We propose a resolution algorithm for the 3-valued paraconsistent logic programming system QMPT0 and its implementation on SWI-Prolog. We also describe an application of the 3-valued paraconsistent logic programming regarding agent decision making.     

Room-temperature fabrication of transparent flexible thin-film transistors using amorphous oxide semiconductors

Transparent electronic devices formed on flexible substrates are expected to meet emerging technological demands where silicon-based electronics cannot provide a solution. Examples of active flexible applications include paper displays and wearable computers. So far, mainly flexible devices based on hydrogenated amorphous silicon (a-Si:H) and organic semiconductors have been investigated. However, the performance of these devices has been insufficient for use as transistors in practical computers and current-driven organic light-emitting diode displays. Fabricating high-performance devices is challenging, owing to a trade-off between processing temperature and device performance. Here, we propose to solve this problem by using a novel semiconducting material--namely, a transparent amorphous oxide semiconductor from the In-Ga-Zn-O system (a-IGZO)--for the active channel in transparent thin-film transistors (TTFTs). The a-IGZO is deposited on polyethylene terephthalate at room temperature and exhibits Hall effect mobilities exceeding 10 cm2 V(-1) s(-1), which is an order of magnitude larger than for hydrogenated amorphous silicon. TTFTs fabricated on polyethylene terephthalate sheets exhibit saturation mobilities of 6-9 cm2 V(-1) s(-1), and device characteristics are stable during repetitive bending of the TTFT sheet.     

Adaptation of photoperiodic control pathways produces short-day flowering in rice

The photoperiodic control of flowering is one of the important developmental processes of plants because it is directly related to successful reproduction. Although the molecular genetic analysis of Arabidopsis thaliana, a long-day (LD) plant, has provided models to explain the control of flowering time in this species, very little is known about its molecular mechanisms for short-day (SD) plants. Here we show how the photoperiodic control of flowering is regulated in rice, a SD plant. Overexpression of OsGI, an orthologue of the Arabidopsis GIGANTEA (GI) gene in transgenic rice, caused late flowering under both SD and LD conditions. Expression of the rice orthologue of the Arabidopsis CONSTANS (CO) gene was increased in the transgenic rice, whereas expression of the rice orthologue of FLOWERING LOCUS T (FT) was suppressed. Our results indicate that three key regulatory genes for the photoperiodic control of flowering are conserved between Arabidopsis, a LD plant, and rice, a SD plant, but regulation of the FT gene by CO was reversed, resulting in the suppression of flowering in rice under LD conditions.