急性腎障害におけるATP動態が、腎予後を規定する

京都大学新制・論文博士博士(医学)乙第13401号論医博第2225号新制||医||1051(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 長船 健二, 教授 渡邊 直樹, 教授 江藤 浩之学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

Unraveling Novel Mechanisms of Neurodegeneration Through a Large-Scale Forward Genetic Screen in Drosophila

Neurodegeneration is characterized by progressive loss of neurons. Genetic and environmental factors both contribute to demise of neurons, leading to diverse devastating cognitive and motor disorders, including Alzheimer’s and Parkinson’s diseases in humans. Over the past few decades, the fruit fly, Drosophila melanogaster, has become an integral tool to understand the molecular, cellular and genetic mechanisms underlying neurodegeneration. Extensive tools and sophisticated technologies allow Drosophila geneticists to identify and study evolutionarily conserved genes that are essential for neural maintenance. In this review, we will focus on a large-scale mosaic forward genetic screen on the fly X-chromosome that led to the identification of a number of essential genes that exhibit neurodegenerative phenotypes when mutated. Most genes identified from this screen are evolutionarily conserved and many have been linked to human diseases with neurological presentations. Systematic electrophysiological and ultrastructural characterization of mutant tissue in the context of the Drosophila visual system, followed by a series of experiments to understand the mechanism of neurodegeneration in each mutant led to the discovery of novel molecular pathways that are required for neuronal integrity. Defects in mitochondrial function, lipid and iron metabolism, protein trafficking and autophagy are recurrent themes, suggesting that insults that eventually lead to neurodegeneration may converge on a set of evolutionarily conserved cellular processes. Insights from these studies have contributed to our understanding of known neurodegenerative diseases such as Leigh syndrome and Friedreich’s ataxia and have also led to the identification of new human diseases. By discovering new genes required for neural maintenance in flies and working with clinicians to identify patients with deleterious variants in the orthologous human genes, Drosophila biologists can play an active role in personalized medicine

The founder sociality hypothesis

創始者社会性仮説は、動物が新しいニッチに進出する際の長期的な社会変化を説明する. 京都大学プレスリリース. 2021-10-29.Founder sociality hypothesis explains long-lasting social change when animals expand into a novel niche. 京都大学プレスリリース. 2021-10-29.In this review, we propose that the social dynamics of founder populations in novel and newly available environments can have critical effects in shaping species' sociality and can produce long-lasting changes in social structure and behavior. For founder populations which expand into an underexploited niche separated from the parent population, the necessity of bond formation with strangers, lack of clear territories, and initial abundance of resources can lead to altered initial social dynamics to which subsequent generations adapt. We call this the founder sociality hypothesis. After specifying the theoretical reasoning and mechanism of effect, we focus on three particular cases where the social dynamics of founder populations may have a central role in explaining their modern behavioral ecology. In particular, we develop and review evidence for three predictions of the founder sociality hypothesis in territorial, mixed-sex group forming species: relatively stronger social bonds in the dispersing sex with relatively weaker bonds in the nondispersing sex, reduced territoriality, and increased social tolerance. We briefly touch on the implications for human evolution given our species' evolutionary history marked by frequent expansion and adaptation to novel environments. We conclude by proposing several experiments and models with testable predictions following from the founder sociality hypothesis

The evolution of group-mindedness: comparative research on top-down and bottom-up group cooperation in bonobos and chimpanzees

Humans engage in a wide variety of group-based cooperation and competition, the cognitive underpinnings of which form "group-mindedness.” The evolutionary basis of these tendencies has attracted significant research from theorists and human-oriented scholars, where evidence suggests a different set of strategies and solutions may be required for explicitly group-based challenges than simply an accumulation of dyadic and triadic solutions embedded in a group setting. We term these top-down and bottom-up group cooperation, respectively. Here, we review previous evolutionary accounts for human group-mindedness, empirical data on bonobos and chimpanzees (focusing on behaviour, cognition, and physiology), and propose a set of future research directions that can help to further our understanding of the evolution of group-mindednes

Resonant Control of Interaction Between Different Electronic States

We observe a magnetic Feshbach resonance in a collision between the ground and metastable states of two-electron atoms of ytterbium (Yb). We measure the on-site interaction of doubly-occupied sites of an atomic Mott insulator state in a three-dimensional optical lattice as a collisional frequency shift in a high-resolution laser spectroscopy. The observed spectra are well fitted by a simple theoretical formula, in which two particles with an s-wave contact interaction are confined in a harmonic trap. This analysis reveals a wide variation of the interaction with a resonance behavior around a magnetic field of about 1.1 Gauss for the energetically lowest magnetic sublevel of ${}^{170}$Yb, as well as around 360 mG for the energetically highest magnetic sublevel of ${}^{174}$Yb. The observed Feshbach resonance can only be induced by an anisotropic inter-atomic interaction. This novel scheme will open the door to a variety of study using two-electron atoms with tunable interaction.Comment: 5 pages, 5 figure

Simultaneous interpretation of KK and BB anomalies in terms of chiral-flavorful vectors

We address the presently reported significant flavor anomalies in the Kaon and $B$ meson systems such as the CP violating Kaon decay ($\epsilon'/\epsilon$) and lepton-flavor universality violation in $B$ meson decays ($R_{K^{(*)}},{R_{D^{(*)}}}$), by proposing flavorful and chiral vector bosons as the new physics constitution at around TeV scale. The chiral-flavorful vectors (CFVs) are introduced as a 63-plet of the global $SU(8)$ symmetry, identified as the one-family symmetry for left-handed quarks and leptons in the standard model (SM) forming the 8-dimensional vector. Thus the CFVs include massive gluons, vector leptoquarks, and $W',Z'$-type bosons, which are allowed to have flavorful couplings with left-handed quarks and leptons, and flavor-universal couplings to right-handed ones, where the latter arises from mixing with the SM gauge bosons. The flavor texture is assumed to possess a "minimal" structure to be consistent with the current flavor measurements on the $K$ and $B$ systems. Among the presently reported significant flavor anomalies in the Kaon and $B$ meson systems ($\epsilon'/\epsilon$, $R_{K^{(*)}}, {R_{D^{(*)}}}$), the first two $\epsilon'/\epsilon$ and $R_{K^{(*)}}$ anomalies can simultaneously be interpreted by the presence of CFVs, the ${R_{D^{(*)}}}$ anomaly is predicted not to survive, due to the approximate $SU(8)$ flavor symmetry. Remarkably, we find that as long as both of the $\epsilon'/\epsilon$ and $R_{K^{(*)}}$ anomalies persist beyond the SM, the CFVs predict the enhanced $K^+ \to \pi^+ \nu \bar{\nu}$ and $K_L \to \pi^0 \nu \bar{\nu}$ decay rates compared to the SM values, which will readily be explored by the NA62 and KOTO experiments, and they will also be explored in new resonance searches at the Large Hadron Collider.Comment: 52 pages, 14 figures, 1 table, version published in JHE