フォワード・ジェネティクスにより同定した新規睡眠覚醒制御遺伝子Sik3 の解析による睡眠覚醒制御機構の解明

筑波大学 (University of Tsukuba)201

フォワード・ジェネティクスにより同定した新規睡眠覚醒制御遺伝子Sik3 の解析による睡眠覚醒制御機構の解明

この博士論文は学術雑誌掲載にて公表予定の内容を含んでいたため、要約のみ公表していましたが、解消したため、平成30(2018)年10月9日に全文を公表しました。筑波大学 (University of Tsukuba)201

Genetic interaction of DISC1 and Neurexin in the development of fruit fly glutamatergic synapses

Originally identified at the breakpoint of a (1;11)(q42.1; q14.3) chromosomal translocation in a Scottish family with a wide range of mental disorders, the DISC1 gene has been a focus of intensive investigations as an entry point to study the molecular mechanisms of diverse mental dysfunctions. Perturbations of the DISC1 functions lead to behavioral changes in animal models, which are relevant to psychiatric conditions in patients. In this work, we have expressed the human DISC1 gene in the fruit fly (Drosophila melanogaster) and performed a genetic screening for the mutations of psychiatric risk genes that cause modifications of DISC1 synaptic phenotypes at the neuromuscular junction. We found that DISC1 interacts with dnrx1, the Drosophila homolog of the human Neurexin (NRXN1) gene, in the development of glutamatergic synapses. While overexpression of DISC1 suppressed the total bouton area on the target muscles and stimulated active zone density in wild-type background, a partial reduction of the dnrx1 activity negated the DISC1–mediated synaptic alterations. Likewise, overexpression of DISC1 stimulated the expression of a glutamate receptor component, DGLURIIA, in wild-type background but not in the dnrx1 heterozygous background. In addition, DISC1 caused mislocalization of Discs large, the Drosophila PSD-95 homolog, in the dnrx1 heterozygous background. Analyses with a series of domain deletions have revealed the importance of axonal localization of the DISC1 protein for efficient suppression of DNRX1 in synaptic boutons. These results thus suggest an intriguing converging mechanism controlled by the interaction of DISC1 and Neurexin in the developing glutamatergic synapses

Artificial Induction of Associative Olfactory Memory by Optogenetic and Thermogenetic Activation of Olfactory Sensory Neurons and Octopaminergic Neurons in Drosophila Larvae

The larval brain of Drosophila melanogaster provides an excellent system for the study of the neurocircuitry mechanism of memory. Recent development of neurogenetic techniques in fruit flies enables manipulations of neuronal activities in freely behaving animals. This protocol describes detailed steps for artificial induction of olfactory associative memory in Drosophila larvae. In this protocol, the natural reward signal is substituted by thermogenetic activation of octopaminergic neurons in the brain. In parallel, the odor signal is substituted by optogenetic activation of a specific class of olfactory receptor neurons. Association of reward and odor stimuli is achieved with the concomitant application of blue light and heat that leads to activation of both sets of neurons in living transgenic larvae. Given its operational simplicity and robustness, this method could be utilized to further our knowledge on the neurocircuitry mechanism of memory in the fly brain

Direct Imaging of Fine Structures in Giant Planet Forming Regions of the Protoplanetary Disk around AB Aurigae

We report high-resolution 1.6 \micron polarized intensity ($PI$) images of the circumstellar disk around the Herbig Ae star AB Aur at a radial distance of 22 AU ($0."15$) up to 554 AU (3.$"$85), which have been obtained by the high-contrast instrument HiCIAO with the dual-beam polarimetry. We revealed complicated and asymmetrical structures in the inner part ($\lesssim$140 AU) of the disk, while confirming the previously reported outer ($r$ $\gtrsim$200 AU) spiral structure. We have imaged a double ring structure at $\sim$40 and $\sim$100 AU and a ring-like gap between the two. We found a significant discrepancy of inclination angles between two rings, which may indicate that the disk of AB Aur is warped. Furthermore, we found seven dips (the typical size is $\sim$45 AU or less) within two rings as well as three prominent $PI$ peaks at $\sim$40 AU. The observed structures, including a bumpy double ring, a ring-like gap, and a warped disk in the innermost regions, provide essential information for understanding the formation mechanism of recently detected wide-orbit ($r$ $>$20 AU) planets.Comment: 12 pages, 3 figure

Imaging of a Transitional Disk Gap in Reflected Light: Indications of Planet Formation Around the Young Solar Analog LkCa 15

We present H- and Ks-band imaging data resolving the gap in the transitional disk around LkCa 15, revealing the surrounding nebulosity. We detect sharp elliptical contours delimiting the nebulosity on the inside as well as the outside, consistent with the shape, size, ellipticity, and orientation of starlight reflected from the far-side disk wall, whereas the near-side wall is shielded from view by the disk's optically thick bulk. We note that forward-scattering of starlight on the near-side disk surface could provide an alternate interpretation of the nebulosity. In either case, this discovery provides confirmation of the disk geometry that has been proposed to explain the spectral energy distributions (SED) of such systems, comprising an optically thick outer disk with an inner truncation radius of ~46 AU enclosing a largely evacuated gap. Our data show an offset of the nebulosity contours along the major axis, likely corresponding to a physical pericenter offset of the disk gap. This reinforces the leading theory that dynamical clearing by at least one orbiting body is the cause of the gap. Based on evolutionary models, our high-contrast imagery imposes an upper limit of 21 Jupiter masses on companions at separations outside of 0.1" and of 13 Jupiter masses outside of 0.2". Thus, we find that a planetary system around LkCa 15 is the most likely explanation for the disk architecture.Comment: 5 pages, 4 figures, accepted for publication in ApJ Letters. Minor change to Figure

Non-linear Mining of Social Activities in Tensor Streams

Web検索履歴等に代表される大規模時系列データは，時刻や地域，キーワードといった様々な情報とともに収集され，テンソルストリームとして扱うことができる．Web上におけるユーザアクティビティの解析では，より高精度な将来予測を実現することが重要な課題の1つであるが，複雑な構造を持つテンソルストリームから将来予測に有用なパターンを発見することが問題となる．本論文では，時間，国，キーワードの3つ組に対するWeb検索数で構成されるテンソルストリームを効果的に解析するためのストリームアルゴリズムであるCUBECASTを提案する．CUBECASTは与えられたテンソルストリームに含まれる潜在的な長期トレンドと季節パターンを発見し，それらを基に類似した特徴を持つ地域グループへと分解する．このとき，提案手法は次の特長を持つ．(a)長期トレンドと季節パターンの非線形特性を単一のモデルで表現する．(b)パラメータチューニングや事前知識を必要とせず，時系列モデルやパターン変化を自動的に推定する．(c)逐次的かつ適応的にパターン変化をとらえ，テンソルストリームを効率的に処理する．実データを用いた実験では，提案手法が将来予測に有用なパターンを効果的かつ効率的に発見できることを示し，既存の時系列予測手法と比較して，予測精度，計算時間の改善を確認した．Given a large time-evolving event series such as Google web-search logs, which are collected according to various aspects, i.e., timestamps, locations and keywords, how accurately can we forecast their future activities? How can we reveal significant patterns that allow us to long-term forecast from such complex tensor streams? In this paper, we propose a streaming method, namely, CUBECAST, that is designed to capture basic trends and seasonality in tensor streams and extract temporal and multi-dimensional relationships between such dynamics. Our proposed method has the following properties: (a) it is effective: it finds both trends and seasonality and summarizes their dynamics into simultaneous non-linear latent space. (b) it is automatic: it automatically recognizes and models such structural patterns without any parameter tuning or prior information. (c) it is scalable: it incrementally and adaptively detects shifting points of patterns for a semi-infinite collection of tensor streams. Extensive experiments that we conducted on real datasets demonstrate that our algorithm can effectively and efficiently find meaningful patterns for generating future values, and outperforms the state-of-the-art algorithms for time series forecasting in terms of forecasting accuracy and computational time

Polarimetric Imaging of Large Cavity Structures in the Pre-transitional Protoplanetary Disk around PDS 70: Observations of the disk

We present high resolution H-band polarized intensity (PI; FWHM = 0."1: 14 AU) and L'-band imaging data (FWHM = 0."11: 15 AU) of the circumstellar disk around the weak-lined T Tauri star PDS 70 in Centaurus at a radial distance of 28 AU (0."2) up to 210 AU (1."5). In both images, a giant inner gap is clearly resolved for the first time, and the radius of the gap is ~70 AU. Our data show that the geometric center of the disk shifts by ~6 AU toward the minor axis. We confirm that the brown dwarf companion candidate to the north of PDS 70 is a background star based on its proper motion. As a result of SED fitting by Monte Carlo radiative transfer modeling, we infer the existence of an optically thick inner disk at a few AU. Combining our observations and modeling, we classify the disk of PDS 70 as a pre-transitional disk. Furthermore, based on the analysis of L'-band imaging data, we put an upper limit mass of companions at ~30 to ~50MJ within the gap. Taking account of the presence of the large and sharp gap, we suggest that the gap could be formed by dynamical interactions of sub-stellar companions or multiple unseen giant planets in the gap.Comment: accepted by APJ