Publications by authors named "Kunio Kawamura"

The role of minerals in the chemical evolution of RNA molecules is an important issue when considering the early stage of the Hadean Earth. In particular, the interaction between functional ribozymes and ancient minerals under simulated primitive conditions is a recent research focus. We are currently attempting to design a primitive RNA metabolic network which would function with minerals, and believe that the simulated chemical network of RNA molecules would be useful for evaluation of the chemical evolution from a simple RNA mixture to an RNA-based life-like system.

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The RNA world hypothesis suggests that chemical networks consisting of functional RNA molecules could have constructed a primitive life-like system leading a first living system. The chemical evolution scenario of RNA molecules should be consistent with the Hadean Earth environment. We have demonstrated the importance of the environment at both high temperature and high pressure, using different types of hydrothermal flow reactor systems and high-pressure equipment.

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Conventional oligopeptide synthesis techniques involve environmentally harmful procedures and materials. In addition, the efficient accumulation of oligopeptides under Hadean Earth environments regarding the origin of life remains still unclear. In these processes, the formation of diketopiperazine is a big issue due to the strong inhibition for further elongation beyond dipeptides.

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Tissue plasminogen activator (t-PA) treatment is beneficial for patients with ischemic stroke within 4.5 h of stroke onset, because the risk of intracerebral hemorrhagic transformation (HT) increases with delayed t-PA treatment. The benefits of t-PA thrombolysis are heavily dependent on time to treatment.

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In a previous study, we have showed that the elongation of an alanine oligopeptide [L-alanyl-L-alanyl-L-alanyl-L-alanine ((Ala))] to higher oligopeptides is enhanced by calcite and dolomite at 275°C, using a mineral-mediated hydrothermal flow reactor system. However, a problem during the use of hydrothermal flow reactor system was that some of the minerals, such as clay, could not be tested due to their clogging in the reactor. In this article, we attempted to analyze the scope of enhancement for the formation of L-alanyl-L-alanyl-L-alanyl-L-alanyl-L-alanine ((Ala)) and higher oligopeptides with different minerals including clay minerals for the elongation of alanine oligopeptide at 175°C.

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Recently, the use of filters has come into light for sanitizing water plants. This study investigated the role of heat-tolerant ultrafilters (UFs) for the remediation of reverse osmosis (RO) plants using periodic thermal disinfection. Two completely identical RO plants (RO plants A and B) were installed in 2006 for surgical hand antisepsis in the operating theater.

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Although studies about the origin of life are a frontier in science and a number of effective approaches have been developed, drawbacks still exist. Examples include: (1) simulation of chemical evolution experiments (which were demonstrated for the first time by Stanley Miller); (2) approaches tracing back the most primitive life-like systems (on the basis of investigations of present organisms); and (3) constructive approaches for making life-like systems (on the basis of molecular biology), such as in vitro construction of the RNA world. Naturally, simulation experiments of chemical evolution under plausible ancient Earth environments have been recognized as a potentially fruitful approach.

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Here we overview the chemical evolution of RNA molecules from inorganic material through mineral-mediated RNA formation compatible with the plausible early Earth environments. Pathways from the gas-phase reaction to the formation of nucleotides, activation and oligomerization of nucleotides, seem to be compatible with specific environments. However, how these steps interacted is not clear since the chemical conditions are frequently different and can be incompatible between them; thus the products would have migrated from one place to another, suitable for further chemical evolution.

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RNA played a central role in the emergence of the first life-like system on primitive Earth since RNA molecules contain both genetic information and catalytic activity. However, there are several drawbacks regarding the RNA world hypothesis. Here, I briefly discuss the feasibility of the RNA world hypothesis to deduce the RNA functions that are essential for forming a life-like system.

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In central nervous system, a growth factor progranulin (PGRN) is considered to play crucial roles in maintaining physiological functions, and mutations in PGRN gene cause TDP-43-positive frontotemporal lobar degeneration. We demonstrated a dynamic change of PGRN expression in ischemic rats, including increased levels of PGRN expression in microglia within the ischemic core, and those in survived neurons as well as induction of PGRN expression in endothelial cells within the ischemic penumbra. We observed that PGRN could protect against acute focal cerebral ischemia by variety of mechanisms, which we call "brain protection", including neuroprotection in part by inhibition of cytoplasmic redistribution of TDP-43 using PGRN knock-out mice, suppression of neuroinflammation via anti-inflammatory interleukin-10 in microglia, and attenuation of blood-brain barrier disruption via vascular endothelial growth factor.

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In the central nervous system, progranulin, a glycoprotein growth factor, plays a crucial role in maintaining physiological functions, and progranulin gene mutations cause TAR DNA-binding protein-43-positive frontotemporal lobar degeneration. Although several studies have reported that progranulin plays a protective role against ischaemic brain injury, little is known about temporal changes in the expression level, cellular localization, and glycosylation status of progranulin after acute focal cerebral ischaemia. In addition, the precise mechanisms by which progranulin exerts protective effects on ischaemic brain injury remains unknown.

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An angiogenesis factor, angiopoietin-1 (Ang1), is associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia. However, whether hemorrhagic transformation and cerebral edema after tissue plasminogen activator (tPA) treatment are related to the decrease in Ang1 expression in the BBB remains unknown. We hypothesized that administering Ang1 might attenuate hemorrhagic transformation and cerebral edema after tPA treatment by stabilizing blood vessels and inhibiting hyperpermeability.

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Unlabelled: This report deals with the construction and management of the reverse osmosis (RO) water system for final rinsing of surgical instruments in the washer-disinfector. Numerous operational challenges were encountered in our RO water system and these were analyzed utilizing the Ishikawa Fishbone diagram. The aim was to find potential problems and promote preventive system management for RO water.

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A new type of flow injection analysis (FIA) combined with a high-temperature reactor maintained at 100-400 °C, namely hydrothermal flow injection analysis (HT-FIA), has been successfully applied to high throughput determination of Ru(III) on the basis of a conventional chromogenic reaction with 1,10-phenothroline (phen). Although this classical chromogenic reaction using phen is sensitive and selective for Ru(III), the complex formation of Ru(phen)(3) requires 2 h. The acceleration using HT-FIA is extraordinary high so that the determination reaction of Ru(III) was successfully shortened to 5 s at 150 °C, where the analytical procedure was accelerated more than 1000-fold.

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The "RNA world" hypothesis proposes that--early in the evolution of life--RNA molecules played important roles both in information storage and in enzymatic functions. However, this hypothesis seems to be inconsistent with the concept that life may have emerged under hydrothermal conditions since RNA molecules are considered to be labile under such extreme conditions. Presently, the possibility that the last common ancestor of the present organisms was a hyperthermophilic organism which is important to support the hypothesis of the hydrothermal origin of life has been subject of strong discussions.

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Following the discovery of ribozymes, the "RNA world" hypothesis has become the most accepted hypothesis concerning the origin of life and genetic information. However, this hypothesis has several drawbacks. Verification of the hypothesis from different viewpoints led us to proposals from the viewpoint of the hydrothermal origin of life, solubility of RNA and related biopolymers, and the possibility of creating an evolutionary system comparable to the in vitro selection technique for functional RNA molecules based on molecular biology.

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To enhance sensitivity and facilitate easy sample introduction into a combinable poly(dimethylsiloxane) (PDMS) capillary (CPC) sensor array, PDMS was modified in bulk and on its surface to prepare "black" PDMS coated with a silver layer and self-assembled monolayer (SAM). India ink, a traditional Japanese black ink, was added to the PDMS pre-polymer for bulk modification. The surface was modified by a silver mirror reaction followed by SAM formation using cysteine.

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To simplify the complicated operation steps and to minimize sample and reagent amounts for enzyme-linked immunosorbent assays (ELISA), we developed a square glass capillary immunosensor containing both covalently immobilized capture antibodies and physically adsorbed enzyme-linked antibodies. The immobilization of capture antibodies (anti-human IgG) was carried out by the treatment of 3-aminopropyltriethoxy silane, glutaraldehyde, and protein-A, followed by affinity capture of the antibody. In contrast, the enzyme-linked antibodies (alkaline phosphatase (ALP)-linked anti-human IgG) were physically adsorbed on the four corners of the capillary with the aid of polyethylene glycol (PEG) acting as a scaffold.

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Article Synopsis
  • - The new combinable poly(dimethyl siloxane) (PDMS) capillary (CPC) sensor simplifies enzyme inhibitor assays by allowing a single-step process where the sample solution initiates a reaction that produces a fluorescence response, making it faster and easier to conduct tests.
  • - The CPC consists of two interlocking PDMS sticks with different coatings that enable the immobilization of reactive reagents like enzymes and substrates, overcoming challenges faced with traditional capillary methods.
  • - By arranging multiple CPCs, the method allows for simultaneous testing of different samples, showcasing its versatility through a successful assay of a protease inhibitor using two independent CPCs.
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Continuous extensive studies on thermophilic organisms have suggested that life emerged on hydrothermal systems on primitive Earth. Thus, it is well known that hydrothermal reactions are, therefore, very important to study fields deeply related to the origin-of-life study. Furthermore, the importance of hydrothermal and solvothermal systems is now realized in both fundamental and practical areas.

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Accumulation of biopolymers should have been an essential step for the emergence of life on primitive Earth. However, experimental simulations for submarine hydrothermal vent systems in which high-temperature water spouts through minerals within a short time scale have not been attempted. Here, we show that enhancement of hydrothermal oligopeptide elongation by naturally occurring minerals was successfully verified for the first time by using a mineral-mediated hydrothermal flow reactor system (MMHF).

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A new type of flow injection analysis (FIA) system combined with an extremely high temperature reactor, namely hydrothermal flow injection analysis (HT-FIA), has been successfully constructed for the first time. Fundamental characteristics of HT-FIA system, such as limit temperature, pressure, and flow rate, were examined as an analytical tool. To demonstrate the potential of HT-FIA, the catalytic activity of Ir(IV) for the degradation of a water-soluble porphyrin, 5,10,15,20-tetraphenyl-21H,23H-porphinetetrasulfonic acid (TPPS), was applied for the determination of trace amounts of Ir(IV).

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International Organization for Standardization (ISO) 15883 for washer-disinfectors has introduced the A(0) concept to allow comparison of the lethality of moist heat processes. The A(0) value is the equivalent disinfection time in seconds at 80 °C calculated on the basis of microbial killing kinetics when the disinfection temperature is over 65 °C. Hepatitis B virus (HBV), transmissible only to humans and chimpanzees, is an important heat-resistant, blood-borne pathogen.

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An angiogenic factor, vascular endothelial growth factor (VEGF), might be associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia; however, it remains unknown whether hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) treatment is related to the activation of VEGF signaling pathway in BBB. Here, we hypothesized that inhibition of VEGF signaling pathway can attenuate HT after tPA treatment. Rats subjected to thromboembolic focal cerebral ischemia were assigned to a permanent ischemia group and groups treated with tPA at 1 or 4 hours after ischemia.

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