ゲノムワイド生存解析により同定された中心性漿液性脈絡網膜症における黄斑新生血管発症とポリープ状脈絡膜血管症との遺伝的背景共有の発見

京都大学新制・課程博士博士(医学)甲第24494号医博第4936号新制||医||1063(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 村川 泰裕, 教授 小杉 眞司, 教授 松田 文彦学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Metamorphic conditions of garnet-bearing gneisses from Niban Rock in the Lutzow-Holm Complex, East Antarctica

The Tenth Symposium on Polar Science/Ordinary sessions: [OG] Polar Geosciences, Wed. 4 Dec. / Entrance Hall (1st floor), National Institute of Polar Researc

Computational Complexity from Learners\u27 Perspective in College Mathematics

—Suitably complex exercises motivate students and facilitates a deeper understanding. Manually constructing suchproblems consumes time that teachers can otherwise use to mentor students. Many software tools and services for automaticgeneration of mathematics problems are available on the web, but they provide only materials up to high school level. In addition, no standardized methods are provided to evaluate and control thecomputational complexity of generated problems. In this paper, we proposed a framework for evaluating computational complex-ity from the learners’ perspective, aiming to apply our framework to the automatic generation of college-level mathematics problems with controlled computational complexity. Our framework helpsteachers prepare learning materials and thereby save time for mentoring students

Effects of chemokine (C–C motif) ligand 1 on microglial function

AbstractMicroglia, which constitute the resident macrophages of the central nervous system (CNS), are generally considered as the primary immune cells in the brain and spinal cord. Microglial cells respond to various factors which are produced following nerve injury of multiple aetiologies and contribute to the development of neuronal disease. Chemokine (C–C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, has been shown to play an important role in neuropathic pain induced by nerve injury and is also produced in various cell types in the CNS, especially in dorsal root ganglia (DRG). However, the role of CCL-1 in the CNS and the effects on microglia remains unclear. Here we showed the multiple effects of CCL-1 on microglia. We first showed that CCR-8, a specific receptor for CCL-1, was expressed on primary cultured microglia, as well as on astrocytes and neurons, and was upregulated in the presence of CCL-1. CCL-1 at concentration of 1ng/ml induced chemotaxis, increased motility at a higher concentration (100ng/ml), and increased proliferation and phagocytosis of cultured microglia. CCL-1 also activated microglia morphologically, promoted mRNA levels for brain-derived neurotrophic factor (BDNF) and IL-6, and increased the release of nitrite from microglia. These indicate that CCL-1 has a role as a mediator in neuron-glia interaction, which may contribute to the development of neurological diseases, especially in neuropathic pain

Development of an experimental method of systematically estimating protein expression limits in HEK293 cells

Protein overexpression sometimes causes cellular defects, although the underlying mechanism is still unknown. A protein's expression limit, which triggers cellular defects, is a useful indication of the underlying mechanism. In this study, we developed an experimental method of estimating the expression limits of target proteins in the human embryonic kidney cell line HEK293 by measuring the proteins' expression levels in cells that survived after the high-copy introduction of plasmid DNA by which the proteins were expressed under a strong cytomegalovirus promoter. The expression limits of nonfluorescent target proteins were indirectly estimated by measuring the levels of green fluorescent protein (GFP) connected to the target proteins with the self-cleaving sequence P2A. The expression limit of a model GFP was similar to 5.0% of the total protein, and sustained GFP overexpression caused cell death. The expression limits of GFPs with mitochondria-targeting signals and endoplasmic reticulum localization signals were 1.6% and 0.38%, respectively. The expression limits of four proteins involved in vesicular trafficking were far lower compared to a red fluorescent protein. The protein expression limit estimation method developed will be valuable for defining toxic proteins and consequences of protein overexpression

Origin of power laws and their spatial fractal structure for city-size distributions

City-size distributions follow an approximate power law in various countries despite high volatility in relative city sizes over time. Our empirical evidence for the United States indicates that the scaling law stems from a spatial fractal structure owing to the coordination of industrial locations. While the locations of individual industries change considerably over time, there is a persistent pattern in that the localized industries at a given time are found only in larger cities. The spatial organization of cities exhibits a stable hierarchical structure in which larger cities are spaced apart to serve as centers for surrounding smaller cities, generating a recursive pattern across different spatial scales. In our theoretical replication of the observed regularities, diversity in scale economy among industries induces diversity in their location pattern, which translates into diversity in city size via spatial coordination of industries and population. The city-size power law is a generic feature of Monte-Carlo samples of stationary states resulting from the spontaneous spatial fractal structure in the hypothetical economy. The identified regularities reveal constraints on feasible urban planning at each regional scale. The success or failure of place-based policies designed to take advantage of individual cities' characteristics should depend on their spatial relationships with other cities, subject to the nationwide spatial fractal structure

High-voltage scanning transmission electron microscopy: A tool for structural characterization of micrometer-thick specimens

Herein, the advantages of high-voltage scanning transmission electron microscopy (STEM) as a tool for structural characterization of micrometer-thick specimens are reported. Dislocations introduced in a wedge-shaped Si crystal were clearly observed by bright-field STEM operating at 1 MV. Many of the dislocations were straight and parallel to the 〈110〉, 〈112〉 or 〈113〉 directions. The widths of the dislocations in the STEM images were almost constant at 13–16 nm (i.e., 4–5 pixels) in the thickness range between 1 and 7.5 µm. The latest high-voltage STEM instrumentation is thus useful for imaging crystal defects in micrometer-thick materials, and enables multi-scale fields of view from a few nanometers squared to over 100 µm2

MACULAR BLOOD FLOW CHANGES IN BRANCH RETINAL VEIN OCCLUSION EXAMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VARIABLE INTERSCAN TIME ANALYSIS

Purpose: To examine the relationship between changes in retinal blood flow and the recurrence of macular edema in eyes with branch retinal vein occlusion. Methods: This observational study included 32 eyes in 32 patients (18 men and 14 women) with branch retinal vein occlusion who visited the Department of Ophthalmology at Kyoto University Hospital (February 2021–November 2021). At the time of inclusion in the study, each patient underwent optical coherence tomography angiography on a macular area measuring 4 × 4 mm2. For variable interscan time analysis, different interscan times were set at 7.6 (IST7.6) and 20.6 ms (IST20.6) for the optical coherence tomography angiography. The parafoveal vessel densities were measured sectorally at IST7.6 and IST20.6, and their relationship with the longitudinal changes evident in the retinal thicknesses during the variable interscan time analysis examination and 2 months later was evaluated. Results: The parafoveal vessel densities in the affected sector was significantly greater at IST20.6 than at IST7.6 (P = 0.011). At 2 months after the variable interscan time analysis examination, 6 patients (19%) showed recurrence of macular edema involving the fovea. The difference in the parafoveal vessel densities (IST20.6 − IST7.6) in the affected sector was significantly associated with longitudinal retinal thickening in the corresponding parafovea (P = 0.020) and fovea (P = 0.014). Conclusion: In eyes with branch retinal vein occlusion, optical coherence tomography angiography variable interscan time analysis facilitated the detection of retinal blood flow changes that might be predictive for the recurrence of macular edema

Implantable pneumatically actuated microsystem for renal pressure-mediated transfection in mice.

In vivo transfection is an important technique used in biological research and drug therapy development. Previously, we developed a renal pressure-mediated transfection method performed by pressing a kidney after an intravenous injection of naked nucleic acids. Although this is a useful method because of its safety and wide range of applications, an innovative approach for performing this method without repeatedly cutting open the abdomen is required. In this study, we developed an implantable microsystem fabricated by Micro-Electro-Mechanical Systems (MEMS) technologies for renal pressure-mediated transfection. The system consists of a polydimethylsiloxane pneumatic balloon actuator (PBA) used as an actuator to press the target kidney. The PBA of the implanted microsystem can be actuated without opening the abdomen by applying air pressure from outside the body to the pressure-supplying port via a needle. We successfully performed renal pressure-mediated transfection using the newly developed system when the implanted system was activated at 60kPa for 10s. This is the first report of an implantable MEMS-based microsystem that demonstrates in vivo transfection to a kidney using naked plasmid DNA