Boso Peninsula, Japan, was formed by the interaction of the Philippine Sea, Eurasian and Pacific plates around the trench–trench–trench Boso triple junction. Normal-type earthquakes are persistently ...observed in the subducting Philippine Sea slab under the peninsula at a depth of ~ 30 km, including a recent (2019)
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4.9 earthquake which caused shaking throughout the Kanto region (greater Tokyo). Such shallow intraplate earthquakes are potentially hazardous to this heavily populated region, yet their mechanism is poorly understood, especially in the context of a three-plate system. Here, we calculate stress rates in the Philippine Sea slab and the surrounding area, using a subduction model constructed in a previous study, to explain the generation of the regional stress field and its effect on earthquake occurrence. In general, the calculated stress rates under Boso Peninsula are horizontally extensional both above and below the Eurasian–Philippine Sea plate interface. We apply our calculated stress rates to the nodal planes of the observed earthquakes to calculate the Coulomb failure function (ΔCFF). These calculated ΔCFFs are generally positive on normal-type earthquakes under Boso. The ΔCFFs are also consistent with earthquakes in adjacent areas that are seismically active, for example, in the Philippine Sea plate to the south, in the collision zone around Izu Peninsula, and in the cluster in the Eurasian plate northeast of Boso Peninsula, which further supports our stress loading model. Calculation of the individual contributions of Philippine Sea plate and Pacific plate subduction shows that the development of the stress field around Boso is dependent upon contributions from both subducting plates. In contrast, the arc–arc collision at Izu Peninsula has little influence.
This paper proposes a technique that increases the lifetime of large scale integration (LSI) devices. As semiconductor technology improves at miniaturizing transistors, aging effects due to bias ...temperature instability (BTI) seriously affects their lifetime. BTI increases the threshold voltage of transistors thereby also increasing the delay of an electronics device, resulting in failures due to timing violations. To compensate for aging-induced timing violations, we exploit configurable approximate computing. Assuming that target circuits have exact and approximate modes, they are configured for the approximate mode if an aging sensor predicts violations. Experiments using an example circuit revealed an increase in its lifetime to >10 years.
Gene delivery using pDNA complexes immobilized on a substrate, termed solid-phase reverse transfection (RTF), has received increasing attention. This is because it can enhance transgene expression ...and localize gene delivery. However, gene carriers used in RTF are limited, and their transgene expression mechanisms are unclear. In this study, we employed pDNA/chitosan/anionic polysaccharide complexes for RTF and investigated their cell transfection mechanisms. The pDNA/chitosan/hyaluronic acid (HA) ternary complexes showed particularly higher transgene expression than other ternary complexes. Cellular uptake and intracellular trafficking pathways were analyzed using inhibitors of endocytosis and intracellular trafficking. It was revealed that pDNA/chitosan/HA complexes were taken up via macropinocytosis and released from late endosomes. Furthermore, pDNA complexes were remarkably accumulated in the nucleus in RTF compared with the conventional forward transfection (FTF) method. These results suggest that the cell transfection efficiency of the pDNA/chitosan/HA ternary complexes in RTF was enhanced by their efficient delivery to the nucleus via late endosomes.We developed pDNA/polysaccharide complexes suitable for reverse transfection (RTF) and investigated their transfection mechanisms. The pDNA/chitosan/hyaluronic acid ternary complexes showed excellent transfection efficiency in RTF compared with the conventional forward transfection (FTF). The ternary complexes were taken up via macropinocytosis in RTF. Furthermore, the ternary complexes in RTF were transported to late endosomes via microtubules, and were remarkably accumulated in the nucleus. These results suggest that the cell transfection efficiency of the ternary complexes in RTF was enhanced by their efficient delivery to the nucleus via late endosomes.
Ganglioside-enriched microdomains in the presynaptic neuronal membrane play a key role in the initiation of amyloid ß-protein (Aß) assembly related to Alzheimer’s disease. We previously isolated ...lipids from a detergent-resistant membrane microdomain fraction of synaptosomes prepared from aged mouse brain and found that spherical Aß assemblies were formed on Aß-sensitive ganglioside nanoclusters (ASIGN) of reconstituted lipid bilayers in the synaptosomal fraction. In the present study, we investigated the role of oligosaccharides in Aß fibril formation induced by ganglioside-containing mixed lipid membranes that mimic the features of ASIGN. Ganglioside nanoclusters were constructed as ternary mixed lipid bilayers composed of ganglioside (GM1, GM2, GM3, GD1a, or GT1b), sphingomyelin, and cholesterol, and their surface topography was visualized by atomic force microscopy. Aß fibril formation on the nanocluster was strongly induced in the presence of 10 mol % ganglioside, and Aß-sensitive features were observed at cholesterol contents of 35–55 mol %. GM1-, GD1a-, and GT1b-containing membranes induced longer fibrils than those containing GD1b and GM2, indicating that the terminal galactose of GM1 along with N-acetylneuraminic acid accelerates protofibril elongation. These results demonstrate that Aß fibril formation is induced by ASIGN that are highly enriched ganglioside nanoclusters with a limited number of components and that the generation and elongation of Aß protofibrils are regulated by the oligosaccharide structure of gangliosides.
In Northeast Japan, it remains a puzzle to reconcile the mismatch between long-term (geological) uplift and late-interseismic and coseismic subsidence associated with the 2011 Tohoku earthquake. To ...explain this mismatch between different periods, we modeled the entire megathrust earthquake cycle in the Northeast Japan arc using a simple dislocation model with a two-layered lithosphere–asthenosphere structure in which we account for viscoelastic relaxation in the asthenosphere and tectonic erosion. The model behaves differently when the rupture stops within the lithosphere and when it cuts through the lithosphere to reach the asthenosphere. It is possible to explain the mismatch in the case where the rupture stops within the lithosphere. In the early interseismic stage, the viscoelastic response to the megathrust earthquake dominates and can compensate for late-interseismic and coseismic subsidence. In contrast, the late-interseismic stage is dominated by the locking effect with the steady slip below the rupture area. Tectonic erosion explains up to about half of the long-term uplift by landward movement of arc topography. The rest of the long-term uplift may be attributed to indirect effects of internal deformation in the arc.
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The levitation methodology, which enables us to operate a contactless reaction without a container, is likely to be a revolutionary technology in the fields of chemistry and biology to reduce the ...plastic waste in life science laboratories. Here, the authors show that plasmid DNA can be effectively transfected into animal cells in a floating droplet of culture medium levitated using ultrasonic standing waves. The data indicate that there is no significant damage to the plasmid and cells during the levitating transfection time, and the transgene expression efficiency and cellular uptake in the droplet are significantly higher than those in the conventional tube, with and without shaking. These results suggest the consolidation of the endocytic uptake pathway into macropinocytosis, indicating that ultrasonic levitation induced a change in cell characteristics. This study suggests that transfection methodology using ultrasonic levitation has the potential to advance the current experimental procedures in the field of cell engineering, in addition to presenting a revolutionary containerless reactor for sustainable technology.
Transfection methodology using ultrasonic levitation has the potential to alter the current experimental process in the area of cell engineering. Herein, it is reported that plasmid DNA can be effectively transfected into animal cells in floating droplets of culture medium levitated using ultrasonic standing waves by consolidation of the endocytic uptake pathway into macropinocytosis.
Motobamide (1), a new cyclic peptide containing a C-prenylated cyclotryptophan residue, was isolated from a marine Leptolyngbya sp. cyanobacterium. Its planar structure was established by ...spectroscopic and MS/MS analyses. The absolute configuration was elucidated based on a combination of chemical degradations, chiral-phase HPLC analyses, spectroscopic analyses, and computational chemistry. Motobamide (1) moderately inhibited the growth of bloodstream forms of Trypanosoma brucei rhodesiense (IC50 2.3 μM). However, it exhibited a weaker cytotoxicity against normal human cells (IC50 55 μM).
Influenza virus (IFV) detection in the early phase of disease is critical for effective anti-influenza therapy using neuraminidase inhibitors. Sialyloligosaccharide receptors on the surface of ...respiratory cells are recognized by IFV hemagglutinin (HA) in the infection. Here, we show that agglutination of IFV is detected using poly(glycidyl methacrylate) (PGMA)-coated polystyrene nanoparticles conjugated with a sialic acid-mimic peptide. The azido peptide was immobilized onto the surface of the PGMA-coated nanoparticles by click chemistry. The distribution of particle size, determined by dynamic light scattering, indicated that the peptide-conjugated nanoparticles were agglutinated in the presence of HA and IFV. Nanoparticles conjugated with the receptor-mimic peptide may be a useful alternative to red blood cells in the global surveillance and clinical diagnosis of influenza.This study examines the use of poly(glycidyl methacrylate) (PGMA)-coated polystyrene functionalized with peptides that mimic receptors found on red blood cells for detection of the influenza virus. Although the current method, the hemagglutination inhibition test, utilized by the World Health Organization, is simple, it has some limitations. We found that our peptide dimers attached to beads were efficiently agglutinated, leading us to detect the presence of the influenza virus antigens. We believe that our study makes a significant contribution to the fight against influenza because we provide an alternative method for the important task of influenza surveillance and diagnosis.
Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated ...by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking. Here, we developed an amphiphilic molecular machine containing a photoresponsive diazocine core (AzoMEx) that localizes in a phospholipid membrane. Upon photoirradiation, AzoMEx expands the liposomal membrane to bias vesicles toward outside-in fission in the membrane deformation process. Cargo components, including micrometer-size M13 bacteriophages that interact with AzoMEx, are efficiently incorporated into the vesicles through the outside-in fission. Encapsulated M13 bacteriophages are transiently protected from the external environment and therefore retain biological activity during distribution throughout the body via the blood following administration. This research developed a molecular approach using synthetic molecular machinery for membrane functionalization to transport micrometer-size substances and objects via vesicle encapsulation. The molecular design demonstrated in this study to expand the membrane for deformation and binding to a cargo component can lead to the development of drug delivery materials and chemical tools for controlling cellular activities.
Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications. In this study, two novel alkyl glycosides, ...Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells. Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion. The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers. For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue. Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments. These results indicate that glycosyltransferases involved in the biosynthesis of mucin-type O-glycans distinguish amino acid residues conjugated to GalNAc. The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
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•Two novel saccharide primers, GalNAc-Ser-C12 and GalNAc-Thr-C12, were synthesized.•O-glycan-type oligosaccharides were obtained by in vitro synthesis using the saccharide primers.•Amino acid selectivity in cellular synthesis of mucin-type O-glycans were observed using the saccharide primers.
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