タンパク質光多量体形成反応を用いた生体内における神経軸索伸長方向の制御の確立

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 小澤 岳昌, 東京大学教授 塩谷 光彦, 東京大学教授 西原 寛, 東京大学教授 菅 裕明, 東京大学准教授 佐藤 守俊University of Tokyo(東京大学

Fruit scent and observer colour vision shape food-selection strategies in wild capuchin monkeys

The senses play critical roles in helping animals evaluate foods, including fruits that can change both in colour and scent during ripening to attract frugivores. Although numerous studies have assessed the impact of colour on fruit selection, comparatively little is known about fruit scent and how olfactory and visual data are integrated during foraging. We combine 25 months of behavioural data on 75 wild, white-faced capuchins (Cebus imitator) with measurements of fruit colours and scents from 18 dietary plant species. We show that frequency of fruit-directed olfactory behaviour is positively correlated with increases in the volume of fruit odours produced during ripening. Monkeys with red-green colour blindness sniffed fruits more often, indicating that increased reliance on olfaction is a behavioural strategy that mitigates decreased capacity to detect red-green colour contrast. These results demonstrate a complex interaction among fruit traits, sensory capacities and foraging strategies, which help explain variation in primate behaviour.https://www.nature.com/articles/s41467-019-10250-9Published versio

Polyphosphate-kinase-1 dependent polyphosphate hyperaccumulation for acclimation to nutrient loss in the cyanobacterium, Synechocystis sp. PCC 6803

Polyphosphate is prevalent in living organisms. To obtain insights into polyphosphate synthesis and its physiological significance in cyanobacteria, we characterize sll0290, a homolog of the polyphosphate-kinase-1 gene, in the freshwater cyanobacterium Synechocystis sp. PCC 6803. The Sll0290 protein structure reveals characteristics of Ppk1. A Synechocystis sll0290 disruptant and sll0290-overexpressing Escherichia coli transformant demonstrated loss and gain of polyphosphate synthesis ability, respectively. Accordingly, sll0290 is identified as ppk1. The disruptant (Δppk1) grows normally with aeration of ordinary air (0.04% CO2), consistent with its photosynthesis comparable to the wild type level, which contrasts with a previously reported high-CO2 (5%) requirement for Δppk1 in an alkaline hot spring cyanobacterium, Synechococcus OS-B’. Synechocystis Δppk1 is defective in polyphosphate hyperaccumulation and survival competence at the stationary phase, and also under sulfur-starvation conditions, implying that sulfur limitation is one of the triggers to induce polyphosphate hyperaccumulation in stationary cells. Furthermore, Δppk1 is defective in the enhancement of total phosphorus contents under sulfur-starvation conditions, a phenomenon that is only partially explained by polyphosphate hyperaccumulation. This study therefore demonstrates that in Synechocystis, ppk1 is not essential for low-CO2 acclimation but plays a crucial role in dynamic P-metabolic regulation, including polyP hyperaccumulation, to maintain physiological fitness under sulfur-starvation conditions

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Advanced Bioluminescence System for In Vivo Imaging with Brighter and Red-Shifted Light Emission

In vivo bioluminescence imaging (BLI), which is based on luminescence emitted by the luciferase–luciferin reaction, has enabled continuous monitoring of various biochemical processes in living animals. Bright luminescence with a high signal-to-background ratio, ideally red or near-infrared light as the emission maximum, is necessary for in vivo animal experiments. Various attempts have been undertaken to achieve this goal, including genetic engineering of luciferase, chemical modulation of luciferin, and utilization of bioluminescence resonance energy transfer (BRET). In this review, we overview a recent advance in the development of a bioluminescence system for in vivo BLI. We also specifically examine the improvement in bioluminescence intensity by mutagenic or chemical modulation on several beetle and marine luciferase bioluminescence systems. We further describe that intramolecular BRET enhances luminescence emission, with recent attempts for the development of red-shifted bioluminescence system, showing great potency in in vivo BLI. Perspectives for future improvement of bioluminescence systems are discussed

Systematic Interrogation of the Temperature Perturbation in the Insulin Signaling Pathway for Optogenetic Stimulation

The application of NIR to optogenetic systems is in great demand due to its superior properties enabling in vivo deep tissue penetration. Irradiation of NIR to tissue samples or cells rapidly generates heat locally. The resultant elevation in temperature affects cells at the molecular level because of the activation of the heat shock pathway and ROS generation. Nevertheless, few reports have presented detailed comparisons of the effects of the temperature change rate on signaling pathway biomolecules, especially those of rapid heat changes. Aiming at broadening the understanding of temperature sensitivity, we investigated seven insulin signaling pathway biomolecules (INSR, IRS1, Akt, GSK3β, p70S6K, FoxO1, and ERK1/2) in three cell lines (C2C12, HepG2, and Fao) at temperatures between 25 and 45 °C. The results show that, except for INSR, pAkt(T308), and FoxO1, biomolecules are sensitive to rapid temperature changes at temperatures higher than 42 °C, at which they are significantly phosphorylated. At 25 °C, around a 50% reduction in phosphorylation occurred. Moreover, p70S6K is sensitive over time. It dephosphorylates quickly (5 min) and then phosphorylates over time. Our findings extend the temperature range to 45 °C, while providing additional time course information about the signaling pathway biomolecule response necessary to advance NIR optogenetic research

Three dimensional analysis of temporomandibular joint and Fossa-Condyle Interspaces in patients with mandibular asymmetry

要旨 緒言 第Ⅰ章下顎側方偏位症例における顎関節形態の三次元的分析 第Ⅱ章下顎側方偏位症例における顎関節隙の三次元的解析 総括 謝辞 参考文献Submitted by QIR アルバイト ([email protected]) on 2010-10-25T04:58:05Z No. of bitstreams: 1 dento_465.pdf: 3960406 bytes, checksum: 4a7605471c6b126bccf5c9d7dca8956c (MD5)Made available in DSpace on 2010-10-25T04:58:06Z (GMT). No. of bitstreams: 1 dento_465.pdf: 3960406 bytes, checksum: 4a7605471c6b126bccf5c9d7dca8956c (MD5) Previous issue date: 2010-03-25顎顔面非対称を有する顎変形症患者においては、その非対称が顎関節にまで及び、下顎頭の形態異常や顎関節症状が高率に発現することが報告されている。また、下顎側方偏位症例では、下顎滑走運動時の動態に非対称を示すことも報告されている。従来、二次元的なX 線写真やCT 断層画像を用いた顎関節部形態の研究は行われているものの、下顎窩と下顎頭の形態、およびその位置関係を三次元的に詳細に調査した研究はない。そこで本研究では、顎変形症患者における下顎側方偏位と顎関節形態および顎関節隙の関連について検討することを目的とし て三次元的形態計測を行った。顎顔面骨格の3D-CT 像から、頭蓋に対する顎関節の位置、大きさ、形態、角度、表面積、および顎関節隙を求め、偏位側と非偏位側について比較検討を行い、以下の結果を得た。下顎頭内外径および下顎頚部の高さは、非偏位側に比べ偏位側において有意に小さい値を示した。下顎窩および下顎頭表面積についても偏位側で有意に小さい値を示し、特に前方内側の領域においてその傾向が強く認められた。また、顎関節隙については、偏位側顎関節の後方外側に下顎頭と下顎窩間の距離が狭い領域が多く認められた。以上の所見より、下顎側方偏位症例では顎関節形態および顎関節隙に非対称が認められ、特に顎関節の前方内側および後方外側において顕著であることが示唆された

Three dimensional analysis of temporomandibular joint and Fossa-Condyle Interspaces in patients with mandibular asymmetry

顎顔面非対称を有する顎変形症患者においては、その非対称が顎関節にまで及び、下顎頭の形態異常や顎関節症状が高率に発現することが報告されている。また、下顎側方偏位症例では、下顎滑走運動時の動態に非対称を示すことも報告されている。従来、二次元的なX 線写真やCT 断層画像を用いた顎関節部形態の研究は行われているものの、下顎窩と下顎頭の形態、およびその位置関係を三次元的に詳細に調査した研究はない。そこで本研究では、顎変形症患者における下顎側方偏位と顎関節形態および顎関節隙の関連について検討することを目的とし て三次元的形態計測を行った。顎顔面骨格の3D-CT 像から、頭蓋に対する顎関節の位置、大きさ、形態、角度、表面積、および顎関節隙を求め、偏位側と非偏位側について比較検討を行い、以下の結果を得た。下顎頭内外径および下顎頚部の高さは、非偏位側に比べ偏位側において有意に小さい値を示した。下顎窩および下顎頭表面積についても偏位側で有意に小さい値を示し、特に前方内側の領域においてその傾向が強く認められた。また、顎関節隙については、偏位側顎関節の後方外側に下顎頭と下顎窩間の距離が狭い領域が多く認められた。以上の所見より、下顎側方偏位症例では顎関節形態および顎関節隙に非対称が認められ、特に顎関節の前方内側および後方外側において顕著であることが示唆された。要旨 緒言 第Ⅰ章下顎側方偏位症例における顎関節形態の三次元的分析 第Ⅱ章下顎側方偏位症例における顎関節隙の三次元的解析 総括 謝辞 参考文