Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment

Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson’s disease

技術の人間化に基づいたサスティナブルデザイン

人類の生存と地球環境が持続可能な社会を目指す「技術の人間化に基づいたサスティナブルデザイン」が注目されている。世界では急速に都市化現象が進み、過度の人工環境が人間生活へ与える影響が懸念されている。例えば、地球温暖化によるヒートアイランド現象が熱中症の増加を促し、さらに過度の照明が生体リズムの乱れと不眠症を誘起している。そこで、ひとの環境適応能力に基づきながら、地球自然環境に多大な負荷を与えない生活環境の構築が不可欠である。第1回シンポジウムでは、ひとにやさしい温熱環境に注目して、ひとと環境のインタラクションについて議論した。次に、災害などの非常事態においても持続可能な社会であり、弱者とされている人々に対する配慮が提供される社会であるべきだという視点から、第2回シンポジウムを企画した。神戸では、多様な地形や自然環境といった地域特性を生かした街づくりと環境未来都市構想について検討がなされている。そこで、第3回シンポジウムでは、ローエネルギーでパッシブな都市デザイン、さらにコミュニティや福祉、観光といったまちづくり戦略について議論を行なった。過剰な技術依存に傾倒する都市計画を再考し、地域の風土・文化特性を生かした都市づくりの情報を発信することをねらいとした。To ensure the survival of humanity and the preservation of the global environment, sustainable design based on the "humanization” of technology is being stressed. Urbanization has proceeded rapidly and the impact of excessive man-made environments on human lifestyles is a concern. For example, the "heat island" phenomenon resulting from global climate change has led to an increase in the number of people suffering from heatstroke. There are few examples of research that focus on both (1) reducing the burden on the earth\u27s natural environment and achieving a recycling-oriented society, which is the starting point for sustainability, and (2) finding ways to build living environments that are based on people\u27s ability to adapt to their environment. We discussed interaction between human being and environment. We also organized a symposium to discuss sustainable design for ensuring the survival of humanity in disaster and social welfare. In Kobe, future city plans have been considered based on regional characteristics. Thus, we investigated low energy-oriented and passive design for city planning

Destruction of Dopaminergic Neurons in the Midbrain by 6-Hydroxydopamine Decreases Hippocampal Cell Proliferation in Rats: Reversal by Fluoxetine

Background Non-motor symptoms (e.g., depression, anxiety, and cognitive deficits) in patients with Parkinson disease (PD) precede the onset of the motor symptoms. Although these symptoms do not respond to pharmacological dopamine replacement therapy, their precise pathological mechanisms are currently unclear. The present study was undertaken to examine whether the unilateral 6-hydroxydopamine (6-OHDA) lesion to the substantia nigra pars compacta (SNc), which represents a model of long-term dopaminergic neurotoxicity, could affect cell proliferation in the adult rat brain. Furthermore, we examined the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the selective noradrenaline reuptake inhibitor maprotiline on the reduction in cell proliferation in the subgranular zone (SGZ) by the unilateral 6-OHDA lesion. Methodology/Principal Findings A single unilateral injection of 6-OHDA into the rat SNc resulted in an almost complete loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and SNc, as well as in reductions of TH-positive cells and fibers in the ventral tegmental area (VTA). On the other hand, an injection of vehicle alone showed no overt change in TH immunoreactivity. A unilateral 6-OHDA lesion to SNc significantly decreased cell proliferation in the SGZ ipsilateral to the 6-OHDA lesion, but not in the contralateral SGZ or the subventricular zone (SVZ), of rats. Furthermore, subchronic (14 days) administration of fluoxetine (5 mg/kg/day), but not maprotiline significantly attenuated the reduction in cell proliferation in the SGZ by unilateral 6-OHDA lesion. Conclusions/Significance The present study suggests that cell proliferation in the SGZ of the dentate gyrus might be, in part, under dopaminergic control by SNc and VTA, and that subchronic administration of fluoxetine reversed the reduction in cell proliferation in the SGZ by 6-OHDA. Therefore, SSRIs such as fluoxetine might be potential therapeutic drugs for non-motor symptoms as well as motor symptoms in patients with PD, which might be associated with the reduction in cell proliferation in the SGZ

技術の人間化に基づいたサステナブルデザイン

本学研究所は、科学技術（工学）と芸術文化の融合をテーマに、人文・社会・自然にまたがる諸科学、および芸術的感性と表現技術を融合し、人類の生活文化を豊かにすることを目標としている。現在、人類の生存と地球環境を持続可能にする社会を作るために、自然環境の保全とともにヒトの適応能力に基づく生活環境の構築が注目されている。今年度は「技術の人間化に基づいたサステナブルデザイン」を課題として、下記の研究を実施した。 １．生体リズムを考慮した快適照明のデザイン ２．福祉とアートのコラボレーション ３．音楽を創るインターフェイス ４．ホスピタル・クラウンにみる笑いの芸術工学 ５．都市のなかのエコロジー：生態学的都市の見方 ６．農業分野に見るユニバーサルデザイン ～機能的で楽しい農作業着のデザインに関する調査研究～ ７．東日本大震災応急仮設住宅の実態調査 ８．デザインウォークinせんだい2011への参加 東日本大震災における神戸芸術工科大学の取り組みCreating a sustainable society that ensures the survival of humanity and the preservation of the global environment will require the achievement of a low-impact way of living based on a new set of values, and the elimination of the causal connection in modern civilization that holds that economic value is produced by the consumption of resources and energy. Design should not simply be understood as a narrow specialty, as it is currently viewed, but instead one that strengthens the relationship with various related domains and strives to create a sustainable society for the survival of humanity and the preservation of the global environment. Sustainable design based on the "humanization” of technology is being stressed as one way to resolve problems with humanity and in society. Particularly indispensable will be the construction of living environments that do not place excessive burden on the planet\u27s natural environment, and are based on the ability of human beings to adapt to natural, man-made and urban environments

Larval pufferfish protected by maternal tetrodotoxin

Marine pufferfish contain tetrodotoxin (TTX), an extremely potent neurotoxin. All species of the genus Takifugu accumulate TTX in the liver and ovaries, although the tissue(s) in which it is localized can differ among species. TTX is the major defense strategy the pufferfish appears to use against predators. TTX is also used as a male-attracting pheromone during spawning. Here we demonstrate an additional (and unexpected) use of maternal TTX in the early larval stages of the Takifugu pufferfish. Predation experiments demonstrated that juveniles of all the species of fish used as predators ingested pufferfish larvae, but spat them out promptly. Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) analysis revealed that the pufferfish larvae contain a small quantity of TTX, which is not enough to be lethal to the predators. Immunohistochemical analysis with anti-TTX monoclonal antibody revealed that the TTX is primarily localized in the body surface of the larvae as a layer of protection. Our study showed the female parent of the Takifugu pufferfish vertically transfers TTX to the larvae through its accumulation in the ovaries, and subsequent localization on the body surface of the larvae

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