Publications by authors named "Masaki Uchida"

103 Publications

Intrinsic coupling between spatially-separated surface Fermi-arcs in Weyl orbit quantum Hall states.

Nat Commun 2021 May 6;12(1):2572. Epub 2021 May 6.

Department of Applied Physics and Quantum-Phase Electronics Center (QPEC), University of Tokyo, Tokyo, Japan.

Topological semimetals hosting bulk Weyl points and surface Fermi-arc states are expected to realize unconventional Weyl orbits, which interconnect two surface Fermi-arc states on opposite sample surfaces under magnetic fields. While the presence of Weyl orbits has been proposed to play a vital role in recent observations of the quantum Hall effect even in three-dimensional topological semimetals, actual spatial distribution of the quantized surface transport has been experimentally elusive. Here, we demonstrate intrinsic coupling between two spatially-separated surface states in the Weyl orbits by measuring a dual-gate device of a Dirac semimetal film. Independent scans of top- and back-gate voltages reveal concomitant modulation of doubly-degenerate quantum Hall states, which is not possible in conventional surface orbits as in topological insulators. Our results evidencing the unique spatial distribution of Weyl orbits provide new opportunities for controlling the novel quantized transport by various means such as external fields and interface engineering.
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http://dx.doi.org/10.1038/s41467-021-22904-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102497PMC
May 2021

Water column gradients beneath the summer ice of a High Arctic freshwater lake as indicators of sensitivity to climate change.

Sci Rep 2021 Feb 3;11(1):2868. Epub 2021 Feb 3.

Centre d'études nordiques, Quebec City, QC, Canada.

Ice cover persists throughout summer over many lakes at extreme polar latitudes but is likely to become increasingly rare with ongoing climate change. Here we addressed the question of how summer ice-cover affects the underlying water column of Ward Hunt Lake, a freshwater lake in the Canadian High Arctic, with attention to its vertical gradients in limnological properties that would be disrupted by ice loss. Profiling in the deepest part of the lake under thick mid-summer ice revealed a high degree of vertical structure, with gradients in temperature, conductivity and dissolved gases. Dissolved oxygen, nitrous oxide, carbon dioxide and methane rose with depth to concentrations well above air-equilibrium, with oxygen values at > 150% saturation in a mid-water column layer of potential convective mixing. Fatty acid signatures of the seston also varied with depth. Benthic microbial mats were the dominant phototrophs, growing under a dim green light regime controlled by the ice cover, water itself and weakly colored dissolved organic matter that was mostly autochthonous in origin. In this and other polar lakes, future loss of mid-summer ice will completely change many water column properties and benthic light conditions, resulting in a markedly different ecosystem regime.
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http://dx.doi.org/10.1038/s41598-021-82234-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858640PMC
February 2021

Delivery of acetaminophen to the central nervous system and the pharmacological effect after intranasal administration with a mucoadhesive agent and absorption enhancer.

Int J Pharm 2021 Feb 11;594:120046. Epub 2020 Dec 11.

Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address:

Acetaminophen, a central antipyretic and analgesic drug, is one of the most commonly used drugs among individuals of all ages throughout the world. This study pharmacokinetically and pharmacodynamically investigated the transport of acetaminophen to the central nervous system and systemic circulation after intranasal (i.n.) administration, and evaluated the potential of a transnasal acetaminophen formulation in comparison to other routes of administration. Direct transport to the brain and the pharmacological effect after the i.n. administration of acetaminophen with polyvinylpyrrolidone (PVP; a mucoadhesive agent) and poly-l-arginine (PLA; an absorption enhancer) were investigated to improve retention of the dosage solution in the olfactory epithelium region and enhance the transfer of acetaminophen to the brain. The transport of acetaminophen to the brain was rapid, and the concentration in the brain, especially the olfactory bulb, was higher after i.n. administration, resulting in a greater antipyretic effect in comparison to other routes of administration. The delivery system using PVP and PLA produced a high and prolonged antipyretic effect by enhancing the transfer of acetaminophen to the brain through suppression of the transfer to systemic circulation. Thus, this transnasal drug delivery system using PVP and PLA may be a promising method for transporting acetaminophen to the brain.
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http://dx.doi.org/10.1016/j.ijpharm.2020.120046DOI Listing
February 2021

Synthetic Virus-like Particles for Glutathione Biosynthesis.

ACS Synth Biol 2020 12 24;9(12):3298-3310. Epub 2020 Nov 24.

Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.

Protein-based nanocompartments found in nature have inspired the development of functional nanomaterials for a range of applications including delivery of catalytic activities with therapeutic effects. As glutathione (GSH) plays a vital role in metabolic adaptation and many diseases are associated with its deficiency, supplementation of GSH biosynthetic activity might be a potential therapeutic when delivered directly to the disease site. Here, we report the successful design and production of active nanoreactors capable of catalyzing the partial or complete pathway for GSH biosynthesis, which was realized by encapsulating essential enzymes of the pathway inside the virus-like particle (VLP) derived from the bacteriophage P22. These nanoreactors are the first examples of nanocages specifically designed for the biosynthesis of oligomeric biomolecules. A dense packing of enzymes is achieved within the cavities of the nanoreactors, which allows us to study enzyme behavior, in a crowded and confined environment, including enzymatic kinetics and protein stability. In addition, the biomedical utility of the nanoreactors in protection against oxidative stress was confirmed using an cell culture model. Given that P22 VLP capsid was suggested as a potential liver-tropic nanocarrier , it will be promising to test the efficacy of these GSH nanoreactors as a novel treatment for GSH-deficient hepatic diseases.
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http://dx.doi.org/10.1021/acssynbio.0c00368DOI Listing
December 2020

Superconductivity in Uniquely Strained RuO_{2} Films.

Phys Rev Lett 2020 Oct;125(14):147001

Department of Applied Physics, University of Tokyo, Tokyo 113-8656, Japan.

We report on strain engineering of superconductivity in RuO_{2} single-crystal films, which are epitaxially grown on rutile TiO_{2} and MgF_{2} substrates with various crystal orientations. Systematic mappings between the superconducting transition temperature and the lattice parameters reveal that shortening of specific ruthenium-oxygen bonds is a common feature among the superconducting RuO_{2} films. Ab initio calculations of electronic and phononic structures for the strained RuO_{2} films suggest the importance of soft phonon modes for emergence of the superconductivity. The findings indicate that simple transition metal oxides such as those with a rutile structure may be suitable for further exploring superconductivity by controlling phonon modes through the epitaxial strain.
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http://dx.doi.org/10.1103/PhysRevLett.125.147001DOI Listing
October 2020

Virus-Like Particles (VLPs) as a Platform for Hierarchical Compartmentalization.

Biomacromolecules 2020 06 5;21(6):2060-2072. Epub 2020 May 5.

Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States.

Hierarchically self-assembled structures are common in biology, but it is often challenging to design and fabricate synthetic analogs. The archetypal cell is defined by hierarchically organized multicompartmentalized structures with boundaries that delineate the interior from exterior environments and is an inspiration for complex functional materials. Here, we have demonstrated an approach to the design and construction of a nested protein cage system that can additionally incorporate the packing of other functional macromolecules and exhibit some of the features of a minimal synthetic cell-like material. We have demonstrated a strategy for controlled co-packaging of subcompartments, ferritin (Fn) cages, together with active cellobiose-hydrolyzing β-glycosidase enzyme macromolecules, CelB, inside the sequestered volume of the bacteriophage P22 capsid. Using controlled assembly, we were able to modulate the stoichiometry of Fn cages and CelB encapsulated inside the P22 to control the degree of compartmentalization. The co-encapsulated enzyme CelB showed catalytic activity even when packaged at high total macromolecular concentrations comparable to an intracellular environment. This approach could be used as a model to create synthetic protein-based protocells that can confine smaller functionalized proto-organelles and additional macromolecules to support a range of biochemical reactions.
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http://dx.doi.org/10.1021/acs.biomac.0c00030DOI Listing
June 2020

Support for fungal infection treatment mediated by pharmacist-led antifungal stewardship activities.

J Infect Chemother 2020 Mar 12;26(3):272-279. Epub 2019 Nov 12.

Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan. Electronic address:

Objective: At the Yokohama General Hospital, pharmacist-led antimicrobial stewardship programs (ASP) including antifungal stewardship programs (AFP) were started in 2012. To investigate the efficacy of the programs, we compared several parameters that are recommended for the measurement of ASP in Japan based on pre- and post-AFP activities.

Patients And Methods: The subjects were inpatients who developed candidemia between April 2008 and March 2016. They were divided into two groups: pre-AFP (April 2008 until March 2012) and post-AFP (April 2012 until March 2016). The results were compared between the two groups.

Results: The cumulative optimal antifungal drug usage rate, as a process parameter, significantly increased in the post-AFP group (p = 0.025). Furthermore, the days of therapy of antifungal drugs in the pre- and post-AFP groups was median 6.0 (interquartile range [IQR] 0.3-15.7) and median 3.4 (IQR 1.9-3.4) per 1,000 patient-days, respectively; there was a significant decrease in the post-AFP group (p < 0.001). Expenditure on antifungal drugs, as an outcome parameter, in the pre- and post-AFP groups was 9390.5 ± 5687.1 and 5930.8 ± 4687.0 US dollars, respectively; there was a significant decrease in the post-AFP group (p = 0.002).

Conclusions: These results suggest that pharmacist-led antifungal stewardship activities improve both outcome and process parameters.
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http://dx.doi.org/10.1016/j.jiac.2019.09.016DOI Listing
March 2020

The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration.

J Clin Invest 2019 09;129(9):3941-3951

Department of Medicine, Indiana University Indianapolis, Indianapolis, Indiana, USA.

Nature exploits cage-like proteins for a variety of biological purposes, from molecular packaging and cargo delivery to catalysis. These cage-like proteins are of immense importance in nanomedicine due to their propensity to self-assemble from simple identical building blocks to highly ordered architecture and the design flexibility afforded by protein engineering. However, delivery of protein nanocages to the renal tubules remains a major challenge because of the glomerular filtration barrier, which effectively excludes conventional size nanocages. Here, we show that DNA-binding protein from starved cells (Dps) - the extremely small archaeal antioxidant nanocage - is able to cross the glomerular filtration barrier and is endocytosed by the renal proximal tubules. Using a model of endotoxemia, we present an example of the way in which proximal tubule-selective Dps nanocages can limit the degree of endotoxin-induced kidney injury. This was accomplished by amplifying the endogenous antioxidant property of Dps with addition of a dinuclear manganese cluster. Dps is the first-in-class protein cage nanoparticle that can be targeted to renal proximal tubules through glomerular filtration. In addition to its therapeutic potential, chemical and genetic engineering of Dps will offer a nanoplatform to advance our understanding of the physiology and pathophysiology of glomerular filtration and tubular endocytosis.
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http://dx.doi.org/10.1172/JCI127511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715384PMC
September 2019

Genetic architecture of leaf photosynthesis in rice revealed by different types of reciprocal mapping populations.

J Exp Bot 2019 10;70(19):5131-5144

Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.

The improvement of leaf net photosynthetic rate (An) is a major challenge in enhancing crop productivity. However, the genetic control of An among natural genetic accessions is still poorly understood. The high-yielding indica cultivar Takanari has the highest An of all rice cultivars, 20-30% higher than that of the high-quality japonica cultivar Koshihikari. By using reciprocal backcross inbred lines and chromosome segment substitution lines derived from a cross between Takanari and Koshihikari, we identified three quantitative trait loci (QTLs) where the Takanari alleles enhanced An in plants with a Koshihikari genetic background and five QTLs where the Koshihikari alleles enhanced An in plants with a Takanari genetic background. Two QTLs were expressed in plants with both backgrounds (type I QTL). The expression of other QTLs depended strongly on genetic background (type II QTL). These beneficial alleles increased stomatal conductance, the initial slope of An versus intercellular CO2 concentration, or An at CO2 saturation. Pyramiding of these alleles consistently increased An. Some alleles positively affected biomass production and grain yield. These alleles associated with photosynthesis and yield can be a valuable tool in rice breeding programs via DNA marker-assisted selection.
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http://dx.doi.org/10.1093/jxb/erz303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6793464PMC
October 2019

Quantized surface transport in topological Dirac semimetal films.

Nat Commun 2019 06 12;10(1):2564. Epub 2019 Jun 12.

Department of Applied Physics and Quantum-Phase Electronics Center (QPEC), University of Tokyo, Tokyo, 113-8656, Japan.

Unconventional surface states protected by non-trivial bulk orders are sources of various exotic quantum transport in topological materials. One prominent example is the unique magnetic orbit, so-called Weyl orbit, in topological semimetals where two spatially separated surface Fermi-arcs are interconnected across the bulk. The recent observation of quantum Hall states in Dirac semimetal CdAs bulks have drawn attention to the novel quantization phenomena possibly evolving from the Weyl orbit. Here we report surface quantum oscillation and its evolution into quantum Hall states in CdAs thin film samples, where bulk dimensionality, Fermi energy, and band topology are systematically controlled. We reveal essential involvement of bulk states in the quantized surface transport and the resultant quantum Hall degeneracy depending on the bulk occupation. Our demonstration of surface transport controlled in film samples also paves a way for engineering Fermi-arc-mediated transport in topological semimetals.
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http://dx.doi.org/10.1038/s41467-019-10499-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561951PMC
June 2019

Characteristics of respiratory muscle fatigue upon inhalation resistance with a maximal inspiratory mouth pressure of 50.

J Phys Ther Sci 2019 Apr 1;31(4):318-325. Epub 2019 Apr 1.

Department of Shizuoka Physical Therapy, Faculty of Health Sciences, Tokoha University:1-30 Mizuochi-cho, Aoi-ku, Shizuoka-shi, Shizuoka 420-0831, Japan.

[Purpose] Considering that respiratory muscle fatigue is a cause of respiratory failure, we aimed to clarify the characteristics of respiratory muscle fatigue under inhalation load and investigate its impact on individual respiratory muscles. [Participants and Methods] The study included 14 healthy adult male volunteers. Maximal inspiratory and expiratory mouth pressures were measured under inhalation load and while at rest. The statuses of the trapezius, sternocleidomastoid, pectoralis major, diaphragm, rectus abdominis, and external and internal abdominal oblique muscles were also assessed using electromyographic frequency analysis. [Results] The maximal inspiratory and expiratory mouth pressures decreased over time and recovered after rest. The median power frequency decreased significantly in the sternocleidomastoid and rectus abdominis muscles at maximal inspiratory and expiratory mouth pressures, respectively, under inhalation load. [Conclusion] As a characteristic of respiratory muscle fatigue, there is a possibility that decreases in maximal inspiratory and expiratory mouth pressures as a result of the inhalation load affect muscle fatigue in the sternocleidomastoid and rectus abdominis muscles.
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http://dx.doi.org/10.1589/jpts.31.318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451961PMC
April 2019

Light quality determines primary production in nutrient-poor small lakes.

Sci Rep 2019 03 15;9(1):4639. Epub 2019 Mar 15.

Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-8563, Japan.

The availability of nutrients for primary producers has long been thought to be the main limiting factor for primary productivity in nutrient-poor lake ecosystems. However, recent studies have indicated that the availability of light energy is also important. On the other hand, the amount of phototroph was reported to decrease in summer in Antarctic lakes, furthermore, the light environment underwater was shown containing high amount of ultraviolet energy in small Antarctic lakes. Here, we hypothesized that primary productivity is limited by not only nutrients and simple light quantity but also light quality in nutrient-poor lakes. Then, we investigate factors influencing primary production by benthic phototrophic communities in shallow nutrient-poor lakes. We examine the relationships between primary production in 17 Antarctic freshwater lakes and nutrient concentrations in lake and benthic water, temperature and light energy. Primary production is decreased by ultraviolet energy reaching the lake bed, showing that production is determined by light quality. We also correlate ultraviolet energy in lake water with the catchment area of each lake. Our results show that the underwater light environment has an important influence on primary production as a key limitation factor and is sensitive to materials in runoff from the surrounding environment for pristine lakes.
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http://dx.doi.org/10.1038/s41598-019-41003-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420600PMC
March 2019

Enhancement Effect of Poly-L-ornithine on the Nasal Absorption of Water-Soluble Macromolecules in Rats.

Biol Pharm Bull 2019 ;42(1):144-148

Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.

The transnasal route for the delivery of water-soluble macromolecules, such as bioactive peptides and proteins, has attracted interest, although the use of permeation enhancers is required due to the poor permeabilities of these macromolecules across the nasal mucosa. With polycationic compounds, such as poly-L-arginine and chitosan, the nasal absorption of hydrophilic macromolecules is molecular weight- and concentration-dependently enhanced without causing cytotoxicity. In the present study, we evaluated the effect of various molecular weights and concentrations of poly-L-ornithine (PLO), a polycationic compound, on the nasal absorption and the damage to the nasal mucosa in vivo. PLO enhanced the nasal absorption of fluorescein isothiocyanate-dextran (FD-4), used as a model drug, and the bioavailability of FD-4 increased with the concentration of PLO. The enhancement effect was also dependent on the molecular weight. The administration of PLO at a concentration that sufficed for enhancing the nasal absorption had no effect on the activity of lactic dehydrogenase and the protein leakage in the nasal fluid, as indices of nasal mucosa damage. These findings suggest that a transnasal delivery system using PLO is a useful strategy for improving the nasal absorption of water-soluble macromolecules without toxicity to the nasal mucosa.
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http://dx.doi.org/10.1248/bpb.b18-00673DOI Listing
April 2019

Mrakia hoshinonis sp. nov., a novel psychrophilic yeast isolated from a retreating glacier on Ellesmere Island in the Canadian High Arctic.

Int J Syst Evol Microbiol 2019 Apr 3;69(4):944-948. Epub 2019 Jan 3.

National Institute of Polar Research (NIPR), 10-3 Midori-cho, Tachikawa, Tokyo 190-8518, Japan.

Four strains isolated from sediment sampled at the front of a retreating glacier on northern Ellesmere Island in the Canadian high Arctic, namely JCM 32575, JCM 32576, JCM 32577 and JCM 32578, belong to a novel psychrophilic basidiomycetous yeast species in the genus Mrakia. Molecular phylogenetic analysis indicated that these strains are most closely related to the type strains of Mrakia aquatica and Mrakianic combsii, but with 8-9 and 7-12 nt substitutions in ITS and in the D1/D2 domain of the LSU rRNA gene, respectively. The strains grew at sub-zero temperatures and in vitamin-free media, with lipase and cellulase highly active even at -3 °C. These characteristics likely allow this yeast species to grow and survive in extremely cold, oligotrophic environments, such as the fronts of retreating glaciers in the high Arctic. The name Mrakia hoshinonis sp. nov. is proposed, with type strain JCM 32575 (UAMH 11969) and MycoBank number MB 825484.
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http://dx.doi.org/10.1099/ijsem.0.003216DOI Listing
April 2019

Vishniacozyma ellesmerensis sp. nov., a psychrophilic yeast isolated from a retreating glacier in the Canadian High Arctic.

Int J Syst Evol Microbiol 2019 Mar 3;69(3):696-700. Epub 2019 Jan 3.

1​National Institute of Polar Research (NIPR), 10-3 Midori-cho, Tachikawa, Tokyo 190-8518, Japan.

Two strains of a psychrophilic basidiomycetous yeast species belonging to the genus Vishniacozyma were isolated from sediments and soil at the front of a retreating glacier on northern Ellesmere Island in the Canadian Arctic. Analysis of the large subunit D1/D2 region and the internal transcribed spacer (ITS) regions of the rDNA indicated that these strains represented a novel species. The closest relatives of the novel species were Vishniacozyma globispora and V. dimennae, which exhibited sequence similarities of 82.2 and 81.6 %, respectively, to the ITS region of the novel species, and contained 61 and 57 nt substitutions, respectively, in the D1/D2 domain, in comparison with the novel species. Strains of the novel species were able to grow at sub-zero temperatures and in vitamin-free medium. These characteristics allow the strains to survive and grow in perennially cold, oligotrophic habitats in the Canadian High Arctic. The name Vishniacozyma ellesmerensis sp. nov. is proposed. The type strain is JCM 32573 (=UAMH 11973=G3-4-8) and the MycoBank number is MB825501.
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http://dx.doi.org/10.1099/ijsem.0.003206DOI Listing
March 2019

Seabird-affected taluses are denitrification hotspots and potential NO emitters in the High Arctic.

Sci Rep 2018 11 22;8(1):17261. Epub 2018 Nov 22.

Institute for Agro-Environmental Sciences, National Agriculture and Food Research Organization, 305-8604, Tsukuba, Japan.

In High Arctic tundra ecosystems, seabird colonies create nitrogen cycling hotspots because of bird-derived labile organic matter. However, knowledge about the nitrogen cycle in such ornithocoprophilous tundra is limited. Here, we determined denitrification potentials and in-situ nitrous oxide (NO) emissions of surface soils on plant-covered taluses under piscivorous seabird cliffs at two sites (BL and ST) near Ny-Ålesund, Svalbard, in the European High Arctic. Talus soils at both locations had very high denitrification potentials at 10 °C (2.62-4.88 mg N kg dry soil h), near the mean daily maximum air temperature in July in Ny-Ålesund, with positive temperature responses at 20 °C (Q10 values, 1.6-2.3). The talus soils contained abundant denitrification genes, suggesting that they are denitrification hotspots. However, high in-situ NO emissions, indicating the presence of both active aerobic nitrification and anaerobic denitrification, were observed only at BL (max. 16.6 µg N m h). Rapid nitrogen turnover at BL was supported by lower carbon-to-nitrogen ratios, higher nitrate content, and higher δN values in the soils at BL compared with those at ST. These are attributed to the 30-fold larger seabird density at BL than at ST, providing the larger organic matter input.
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http://dx.doi.org/10.1038/s41598-018-35669-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250683PMC
November 2018

[Gender Differences in Projected Life Expectancy in Japan (2023-2047) Determined by Bayesian Age-Period-Cohort Analysis].

Nihon Eiseigaku Zasshi 2018 ;73(3):338-353

Division of Clinical Dietetics and Human Nutrition, Graduate School of Pharmaceutical Sciences, Josai University.

Objectives: In this study, we aimed to (1) determine the effects of age, period, and cohort on mortality rate trends between 1958 and 2012 in Japan and (2) assess gender differences in projected life expectancy (LE) for the 2023-2047 period.

Methods: A time trend study was conducted using age-period-cohort (APC) analysis. A Bayesian APC model was fitted to describe mortality rate trends for the 1958-2012 period and to project mortality rates for 2023-2047. LE was predicted by Chiang's method using projected mortality rates.

Results: Age, period, and cohort effects showed similar patterns between males and females. As time passes, gender differences in projected LE were larger among individuals over 65 years than among those under 65 years. Time series change rates of the extension of projected LE after excluding specific causes of death showed the following: smaller extension of projected LE in males in terms of mortality risk from malignant neoplasms, heart diseases, pneumonia, and accidents (under 65 years) and in females in terms of mortality risk from heart diseases, cerebrovascular diseases, and suicide (over 65 years).

Conclusions: Gender differences in projected LE are expected to be smaller before middle age and to be larger among seniors. These projected gender differences stem in part from the lower mortality risk among men than among women from malignant neoplasms, heart diseases, pneumonia, and accidents (under 65 years), and among women compared to men from heart disease, cerebrovascular disease, and suicide (over 65 years).
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http://dx.doi.org/10.1265/jjh.73.338DOI Listing
October 2018

Gate-tuned quantum Hall states in Dirac semimetal (Cd Zn )As.

Sci Adv 2018 05 18;4(5):eaar5668. Epub 2018 May 18.

Department of Applied Physics and Quantum-Phase Electronics Center (QPEC), University of Tokyo, Tokyo 113-8656, Japan.

The recent discovery of topological Dirac semimetals (DSMs) has provoked intense curiosity not only regarding Weyl physics in solids but also about topological phase transitions originating from DSMs. One specific area of interest is controlling the dimensionality to realize two-dimensional quantum phases such as quantum Hall and quantum spin Hall states. For investigating these phases, the Fermi level is a key controlling parameter. From this perspective, we report the carrier density control of quantum Hall states realized in thin films of DSM CdAs. Chemical doping of Zn combined with electrostatic gating has enabled us to tune the carrier density both over a wide range and continuously, even across the charge neutrality point. Comprehensive analyses of gate-tuned quantum transport have revealed Landau-level formation from linearly dispersed sub-bands and its contribution to the quantum Hall states. Our findings also pave the way for investigating the low-energy physics near the Dirac points of DSMs.
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http://dx.doi.org/10.1126/sciadv.aar5668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959317PMC
May 2018

Templated Assembly of a Functional Ordered Protein Macromolecular Framework from P22 Virus-like Particles.

ACS Nano 2018 04 26;12(4):3541-3550. Epub 2018 Mar 26.

Department of Chemistry , Indiana University , 800 East Kirkwood Avenue , Bloomington , Indiana 47405 , United States.

Bottom-up construction of mesoscale materials using biologically derived nanoscale building blocks enables engineering of desired physical properties using green production methods. Virus-like particles (VLPs) are exceptional building blocks due to their monodispersed sizes, geometric shapes, production ease, proteinaceous composition, and our ability to independently functionalize the interior and exterior interfaces. Here a VLP, derived from bacteriophage P22, is used as a building block for the fabrication of a protein macromolecular framework (PMF), a tightly linked 3D network of functional protein cages that exhibit long-range order and catalytic activity. Assembly of PMFs was electrostatically templated, using amine-terminated dendrimers, then locked into place with a ditopic cementing protein that binds to P22. Long-range order is preserved on removal of the dendrimer, leaving a framework material composed completely of protein. Encapsulation of β-glucosidase enzymes inside of P22 VLPs results in formation of stable, condensed-phase materials with high local concentration of enzymes generating catalytically active PMFs.
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http://dx.doi.org/10.1021/acsnano.8b00528DOI Listing
April 2018

Protein cage assembly across multiple length scales.

Chem Soc Rev 2018 May;47(10):3433-3469

Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.

Within the materials science community, proteins with cage-like architectures are being developed as versatile nanoscale platforms for use in protein nanotechnology. Much effort has been focused on the functionalization of protein cages with biological and non-biological moieties to bring about new properties of not only individual protein cages, but collective bulk-scale assemblies of protein cages. In this review, we report on the current understanding of protein cage assembly, both of the cages themselves from individual subunits, and the assembly of the individual protein cages into higher order structures. We start by discussing the key properties of natural protein cages (for example: size, shape and structure) followed by a review of some of the mechanisms of protein cage assembly and the factors that influence it. We then explore the current approaches for functionalizing protein cages, on the interior or exterior surfaces of the capsids. Lastly, we explore the emerging area of higher order assemblies created from individual protein cages and their potential for new and exciting collective properties.
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http://dx.doi.org/10.1039/c7cs00818jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729141PMC
May 2018

Structural characterisation of high-mobility CdAs films crystallised on SrTiO.

Sci Rep 2018 02 2;8(1):2244. Epub 2018 Feb 2.

Department of Applied Physics and Quantum-Phase Electronics Center (QPEC), the University of Tokyo, Tokyo, 113-8656, Japan.

CdAs has long been known as a high-mobility semiconductor. The recent finding of a topological semimetal state in this compound has demanded growth of epitaxial films with high crystallinity and controlled thickness. Here we report the structural characterisation of CdAs films grown on SrTiO substrates by solid-phase epitaxy at high temperatures up to 600 °C by employing optimised capping layers and substrates. The As triangular lattice is epitaxially stacked on the Ti square lattice of the (001) SrTiO substrate, producing (112)-oriented CdAs films exhibiting high crystallinity with a rocking-curve width of 0.02° and a high electron mobility exceeding 30,000 cm/Vs. The systematic characterisation of films annealed at various temperatures allowed us to identify two-step crystallisation processes in which out-of-plane and subsequently in-plane directions occur with increasing annealing temperature. Our findings on the high-temperature crystallisation process of CdAs enable a unique approach for fabricating high-quality CdAs films and elucidating quantum transport by back gating through the SrTiO substrate.
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http://dx.doi.org/10.1038/s41598-018-20758-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797121PMC
February 2018

Improved Intranasal Retentivity and Transnasal Absorption Enhancement by PEGylated Poly-l-ornithine.

Pharmaceuticals (Basel) 2018 Jan 25;11(1). Epub 2018 Jan 25.

Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.

We reported that the introduction of polyethylene glycol (PEG) to poly-l-ornithine (PLO), which is an homopolymeric basic amino acid having absorption-enhancement ability, prolonged retention time in an in vitro inclined plate test, probably due to an increase in viscosity caused by PEGylation. The aim of the present study is to investigate whether the introduction of PEG chains to PLO improves intranasal retention and transnasal absorption in vivo. We performed intranasal administration experiments using PLO and PEG-PLO with a model drug, fluorescein isothiocyanate dextran (FD-4), in rats under closed and open systems. In the open system, transition of plasma FD-4 concentration after co-administration with unmodified PLO was low, and the area under the plasma concentration-time curve (AUC) decreased to about 60% of that in the closed system. In contrast, the AUC after co-administration with PEG-PLO in the open system was about 90% of that in the closed system, and the transition of plasma FD-4 concentration and FD-4 absorption profile were similar to those of the closed system. These findings indicate that introducing PEG chains to homopolymeric basic amino acids (HPBAAs) is a very useful method for developing a functional absorption enhancer that can exhibit an efficient in vivo absorption-enhancing effect.
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http://dx.doi.org/10.3390/ph11010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874705PMC
January 2018

Electric-field control of anomalous and topological Hall effects in oxide bilayer thin films.

Nat Commun 2018 01 15;9(1):213. Epub 2018 Jan 15.

Department of Applied Physics and Quantum-Phase Electronics Center (QPEC), University of Tokyo, Tokyo, 113-8656, Japan.

One of the key goals in spintronics is to tame the spin-orbit coupling (SOC) that links spin and motion of electrons, giving rise to intriguing magneto-transport properties in itinerant magnets. Prominent examples of such SOC-based phenomena are the anomalous and topological Hall effects. However, controlling them with electric fields has remained unachieved since an electric field tends to be screened in itinerant magnets. Here we demonstrate that both anomalous and topological Hall effects can be modulated by electric fields in oxide heterostructures consisting of ferromagnetic SrRuO and nonmagnetic SrIrO. We observe a clear electric field effect only when SrIrO is inserted between SrRuO and a gate dielectric. Our results establish that strong SOC of nonmagnetic materials such as SrIrO is essential in electrical tuning of these Hall effects and possibly other SOC-related phenomena.
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http://dx.doi.org/10.1038/s41467-017-02629-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768777PMC
January 2018

The effect of tar spot pathogen on host plant carbon balance and its possible consequences on a tundra ecosystem.

Oecologia 2018 03 22;186(3):843-853. Epub 2017 Dec 22.

National Institute of Polar Research, 10-3 Midori-cho, Tachikawa, Tokyo, 190-8518, Japan.

In Arctic tundra, plant pathogens have substantial effects on the growth and survival of hosts, and impacts on the carbon balance at the scale of ecological systems. To understand these effects on carbon dynamics across different scales including plant organ, individual, population and ecosystem, we focused on two primary factors: host productivity reduction and carbon consumption by the pathogen. We measured the effect of the pathogen on photosynthetic and respiratory activity in the host. We also measured respiration and the amount of carbon in the pathogen. We constructed a model based on these two factors, and calculated pathogenic effects on the carbon balance at different organismal and ecological scales. We found that carbon was reduced in infected leaves by 118% compared with healthy leaves; the major factor causing this loss was pathogenic carbon consumption. The carbon balance at the population and ecosystem levels decreased by 35% and 20%, respectively, at an infection rate of 30%. This case study provides the first evidence that a host plant can lose more carbon through pathogenic carbon consumption than through a reduction in productivity. Such a pathogenic effect could greatly change ecosystem carbon cycling without decreasing annual productivity.
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http://dx.doi.org/10.1007/s00442-017-4037-7DOI Listing
March 2018

Quantum Hall states observed in thin films of Dirac semimetal CdAs.

Nat Commun 2017 12 22;8(1):2274. Epub 2017 Dec 22.

Department of Applied Physics and Quantum-Phase Electronics Center (QPEC), the University of Tokyo, Tokyo, 113-8656, Japan.

A well known semiconductor CdAs has reentered the spotlight due to its unique electronic structure and quantum transport phenomena as a topological Dirac semimetal. For elucidating and controlling its topological quantum state, high-quality CdAs thin films have been highly desired. Here we report the development of an elaborate growth technique of high-crystallinity and high-mobility CdAs films with controlled thicknesses and the observation of quantum Hall effect dependent on the film thickness. With decreasing the film thickness to 10 nm, the quantum Hall states exhibit variations such as a change in the spin degeneracy reflecting the Dirac dispersion with a large Fermi velocity. Details of the electronic structure including subband splitting and gap opening are identified from the quantum transport depending on the confinement thickness, suggesting the presence of a two-dimensional topological insulating phase. The demonstration of quantum Hall states in our high-quality CdAs films paves a road to study quantum transport and device application in topological Dirac semimetal and its derivative phases.
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http://dx.doi.org/10.1038/s41467-017-02423-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741620PMC
December 2017

Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis.

ACS Nano 2018 02 20;12(2):942-953. Epub 2017 Nov 20.

Department of Chemistry, Indiana University , 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States.

The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here, we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy: the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from an amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme-packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. This study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales and exhibits properties and function that arise from the interaction between individual building blocks.
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http://dx.doi.org/10.1021/acsnano.7b06049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870838PMC
February 2018

Modular interior loading and exterior decoration of a virus-like particle.

Nanoscale 2017 Jul;9(29):10420-10430

Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, USA.

Virus-like particles (VLPs) derived from the bacteriophage P22 offer an interesting and malleable platform for encapsulation and multivalent presentation of cargo molecules. The packaging of cargo in P22 VLP is typically achieved through genetically enabled directed in vivo encapsulation. However, this approach does not allow control over the packing density and composition of the encapsulated cargos. Here, we have adopted an in vitro assembly approach to gain control over cargo packaging in P22. The packaging was controlled by closely regulating the stoichiometric ratio of cargo-fused-scaffold protein and wild-type scaffold protein during the in vitro assembly. In a "one-pot assembly reaction" coat protein subunits were incubated with varied ratios of wild-type scaffold protein and cargo-fused-scaffold protein, which resulted in the encapsulation of both components in a co-assembled capsid. These experiments demonstrate that an input stoichiometry can be used to achieve controlled packaging of multiple cargos within the VLP. The porous nature of P22 allows the escape and re-entry of wild-type scaffold protein from the assembled capsid but scaffold protein fused to a protein-cargo cannot traverse the capsid shell due to the size of the cargo. This has allowed us to control and alter the packing density by selectively releasing wild-type scaffold protein from the co-assembled capsids. We have demonstrated these concepts in the P22 system using an encapsulated streptavidin protein and have shown its highly selective interaction with biotin or biotin derivatives. Additionally, this system can be used to encapsulate small molecules coupled to biotin, or display large proteins, that cannot enter the capsid and thus remain available for the multivalent display on the exterior of the capsid when attached to a flexible biotinylated linker. Thus, we have developed a P22 system with controlled protein cargo composition and packing density, to which both small and large molecules can be attached at high copy number on the interior or exterior of the capsid.
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http://dx.doi.org/10.1039/c7nr03018eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482854PMC
July 2017

Sortase-Mediated Ligation as a Modular Approach for the Covalent Attachment of Proteins to the Exterior of the Bacteriophage P22 Virus-like Particle.

Bioconjug Chem 2017 08 30;28(8):2114-2124. Epub 2017 Jun 30.

Department of Chemistry, Indiana University , Bloomington, Indiana 47407, United States.

Virus-like particles are unique platforms well suited for the construction of nanomaterials with broad-range applications. The research presented here describes the development of a modular approach for the covalent attachment of protein domains to the exterior of the versatile bacteriophage P22 virus-like particle (VLP) via a sortase-mediated ligation strategy. The bacteriophage P22 coat protein was genetically engineered to incorporate an LPETG amino acid sequence on the C-terminus, providing the peptide recognition sequence utilized by the sortase enzyme to catalyze peptide bond formation between the LPETG-tagged protein and a protein containing a polyglycine sequence on the N-terminus. Here we evaluate attachment of green fluorescent protein (GFP) and the head domain of the influenza hemagglutinin (HA) protein by genetically producing polyglycine tagged proteins. Attachment of both proteins to the exterior of the P22 VLP was found to be highly efficient as judged by SDS-PAGE densitometry. These results enlarge the tool kit for modifying the P22 VLP system and provide new insights for other VLPs that have an externally displayed C-terminus that can use the described strategy for the modular modification of their external surface for various applications.
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http://dx.doi.org/10.1021/acs.bioconjchem.7b00296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708598PMC
August 2017

Dietary nitrite supplementation attenuates cardiac remodeling in l-NAME-induced hypertensive rats.

Nitric Oxide 2017 Jul 21;67:1-9. Epub 2017 Apr 21.

Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan. Electronic address:

Loss of nitric oxide (NO) bioavailability underlies the development of hypertensive heart disease. We investigated the effects of dietary nitrite on N-nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Sprague-Dawley rats were divided into five groups: an untreated control group, an l-NAME-treated group, and three other l-NAME-treated groups supplemented with 10 mg/L or 100 mg/L of nitrite or 100 mg/L of captopril in drinking water. After the 8-week experimental period, mean arterial blood pressure was measured, followed by sampling of blood and heart tissue for assessment of nitrite/nitrate levels in the plasma and heart, the plasma level of angiotensin II (AT II), and the heart transcriptional levels of AT II type 1 receptor (ATR), transforming growth factor-β1 (TGF-β1), and connective tissue proteins such as type 1 collagen and fibronectin. Heart tissue was analyzed by histopathological morphometry, including assessments of ventricular and coronary vascular hypertrophy and fibrosis, as well as immunohistochemistry analyses of myocardial expression of ATR. l-NAME treatment reduced the plasma nitrate level and led to the development of hypertension, with increased plasma levels of AT II and increased heart transcriptional levels of ATR and TGF-β1-mediated connective tissue proteins, showing myocardial and coronary arteriolar hypertrophy and fibrosis. However, dietary nitrite supplementation inhibited TGF-β1-mediated cardiac remodeling by suppressing AT II and ATR. These results suggest that dietary nitrite levels achievable via a daily high-vegetable diet could improve hypertensive heart disease by inhibiting AT II-ATR-mediated cardiac remodeling.
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http://dx.doi.org/10.1016/j.niox.2017.04.009DOI Listing
July 2017

Preparation and Evaluation of PEGylated Poly-L-ornithine Complex as a Novel Absorption Enhancer.

Biol Pharm Bull 2017 ;40(2):205-211

Faculty of Pharmaceutical Sciences, Josai University.

Polycationic compounds, such as poly-L-arginine and poly-L-ornithine (PLO), enhance the nasal absorption of hydrophilic macromolecular drugs. However, the bio availability corresponding to the dose of these enhancers has not been obtained in an open system study, where an administered solution is transferred to the pharynx because they do not exhibit mucoadhesion/retention in the nasal cavity. In this study, we prepared PEGylated-poly-L-ornithine (PEG-PLO) and investigated the effects of PEGylation on in vitro adhesion/retention properties, permeation enhancement efficiency, and cytotoxicity. PEG-PLO bearing 3-4 polyethylene glycol (PEG) chains per PLO molecule was more retentive than unmodified PLO on an inclined plate. The permeability of a model drug, FD-4, across Caco-2 cell sheets was enhanced by PEG-PLO as well as by PLO. PLO showed cytotoxicity at high concentrations, whereas PEG-PLO did not decrease cell viability, even above the concentration giving a sufficient enhancement effect. These findings suggest that PEGylation of polycationic absorption enhancers improves their adhesion/retention and decreases their cytotoxicity, which may lead to enhancers with greater utility.
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http://dx.doi.org/10.1248/bpb.b16-00781DOI Listing
February 2017