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Showing papers by "Tokyo University of Science published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
TL;DR: In this paper, the photocatalyst sheet design enables efficient and scalable water splitting using particulate semiconductors, which is a potentially scalable and economically feasible technology for converting solar energy into hydrogen.
Abstract: Photocatalytic water splitting using semiconductors is attractive for converting solar energy into hydrogen. An efficient and scalable system based on particulate photocatalyst sheets is now shown to exhibit energy conversion efficiency exceeding 1%. Photocatalytic water splitting using particulate semiconductors is a potentially scalable and economically feasible technology for converting solar energy into hydrogen1,2,3. Z-scheme systems based on two-step photoexcitation of a hydrogen evolution photocatalyst (HEP) and an oxygen evolution photocatalyst (OEP) are suited to harvesting of sunlight because semiconductors with either water reduction or oxidation activity can be applied to the water splitting reaction4,5. However, it is challenging to achieve efficient transfer of electrons between HEP and OEP particles6,7. Here, we present photocatalyst sheets based on La- and Rh-codoped SrTiO3 (SrTiO3:La, Rh; ref. 8) and Mo-doped BiVO4 (BiVO4:Mo) powders embedded into a gold (Au) layer. Enhancement of the electron relay by annealing and suppression of undesirable reactions through surface modification allow pure water (pH 6.8) splitting with a solar-to-hydrogen energy conversion efficiency of 1.1% and an apparent quantum yield of over 30% at 419 nm. The photocatalyst sheet design enables efficient and scalable water splitting using particulate semiconductors.

1,190 citations


Journal ArticleDOI
TL;DR: The technique enables direct 3D fabrication without the use of molds and may become the standard next-generation composite fabrication methodology.
Abstract: We have developed a method for the three-dimensional (3D) printing of continuous fiber-reinforced thermoplastics based on fused-deposition modeling. The technique enables direct 3D fabrication without the use of molds and may become the standard next-generation composite fabrication methodology. A thermoplastic filament and continuous fibers were separately supplied to the 3D printer and the fibers were impregnated with the filament within the heated nozzle of the printer immediately before printing. Polylactic acid was used as the matrix while carbon fibers, or twisted yarns of natural jute fibers, were used as the reinforcements. The thermoplastics reinforced with unidirectional jute fibers were examples of plant-sourced composites; those reinforced with unidirectional carbon fiber showed mechanical properties superior to those of both the jute-reinforced and unreinforced thermoplastics. Continuous fiber reinforcement improved the tensile strength of the printed composites relative to the values shown by conventional 3D-printed polymer-based composites.

722 citations


Journal ArticleDOI
Felix Aharonian1, Felix Aharonian2, Hiroki Akamatsu3, Fumie Akimoto4  +221 moreInstitutions (60)
06 Jul 2016-Nature
TL;DR: X-ray observations of the core of the Perseus cluster reveal a remarkably quiescent atmosphere in which the gas has a line-of-sight velocity dispersion of 164 ± 10 kilometres per second in the region 30–60 kiloparsecs from the central nucleus, infering that a total cluster mass determined from hydrostatic equilibrium in a central region would require little correction for turbulent pressure.
Abstract: The Hitomi collaboration reports X-ray observations of the core of the Perseus cluster of galaxies the brightest X-ray-emitting cluster in the sky. Such clusters typically consist of tens to thousands of galaxies bound together by gravity and are studied as models of both small-scale cosmology and large-scale astrophysical processes. The data reveal a remarkably quiescent atmosphere, where gas velocities are quite low, with a line-of-sight velocity dispersion of about 164 kilometres per second at a distance of 3060 kiloparsecs from the central nucleus.

449 citations


Journal ArticleDOI
TL;DR: P powdered Z-schematic water splitting under visible light and simulated sunlight irradiation is demonstrated by combining metal sulfides as an H2-evolving photocatalyst, reduced graphene oxide (RGO) as an electron mediator, and a visible-light-driven BiVO4 as an O2- Evolving photoc atalyst.
Abstract: Metal sulfides are highly active photocatalysts for water reduction to form H2 under visible light irradiation, whereas they are unfavorable for water oxidation to form O2 because of severe self-photooxidation (i.e., photocorrosion). Construction of a Z-scheme system is a useful strategy to split water into H2 and O2 using such photocorrosive metal sulfides because the photogenerated holes in metal sulfides are efficiently transported away. Here, we demonstrate powdered Z-schematic water splitting under visible light and simulated sunlight irradiation by combining metal sulfides as an H2-evolving photocatalyst, reduced graphene oxide (RGO) as an electron mediator, and a visible-light-driven BiVO4 as an O2-evolving photocatalyst. This Z-schematic photocatalyst composite is also active in CO2 reduction using water as the sole electron donor under visible light.

415 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the suppression of formation of superoxide-like species on lithium extraction results in reversible redox for oxide ions, which is stabilized by the presence of relatively less covalent character of Mn4+ with oxide ions without the sacrifice of electronic conductivity.
Abstract: Further increase in energy density of lithium batteries is needed for zero emission vehicles. However, energy density is restricted by unavoidable theoretical limits for positive electrodes used in commercial applications. One possibility towards energy densities exceeding these limits is to utilize anion (oxide ion) redox, instead of classical transition metal redox. Nevertheless, origin of activation of the oxide ion and its stabilization mechanism are not fully understood. Here we demonstrate that the suppression of formation of superoxide-like species on lithium extraction results in reversible redox for oxide ions, which is stabilized by the presence of relatively less covalent character of Mn4+ with oxide ions without the sacrifice of electronic conductivity. On the basis of these findings, we report an electrode material, whose metallic constituents consist only of 3d transition metal elements. The material delivers a reversible capacity of 300 mAh g-1 based on solid-state redox reaction of oxide ions.

303 citations


Journal ArticleDOI
15 Mar 2016-Immunity
TL;DR: This work explored the population dynamics of genetically diverse GC responses to two complex antigens-Bacillus anthracis protective antigen and influenza hemagglutinin-in which B cells competed both intra- and interclonally for distinct epitopes.

250 citations


Journal ArticleDOI
TL;DR: A novel role is identified for IL-17-producing γδ T cells in skeletal tissue regeneration by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells and promoting bone formation and bone fracture healing.
Abstract: Immune responses are crucial not only for host defence against pathogens but also for tissue maintenance and repair after injury. Lymphocytes are involved in the healing process after tissue injury, including bone fracture and muscle damage. However, the specific immune cell subsets and mediators of healing are not entirely clear. Here we show that γδ T cells produce IL-17A, which promotes bone formation and facilitates bone fracture healing. Repair is impaired in IL-17A-deficient mice due to a defect in osteoblastic bone formation. IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells. This study identifies a novel role for IL-17-producing γδ T cells in skeletal tissue regeneration.

248 citations


Journal ArticleDOI
TL;DR: In this article, surface characterization techniques are combined for investigation on the electrode/electrolyte interface of the black phosphorus electrodes with polyacrylate binder to understand the formation of a solid electrolyte interphase (SEI) in alkyl carbonate ester and its evolution during cycling.
Abstract: For a nonaqueous sodium-ion battery (NIB), phosphorus materials have been studied as the highest-capacity negative electrodes. However, the large volume change of phosphorus upon cycling at low voltage causes the formation of new active surfaces and potentially results in electrolyte decomposition at the active surface, which remains one of the major limiting factors for the long cycling life of batteries. In this present study, powerful surface characterization techniques are combined for investigation on the electrode/electrolyte interface of the black phosphorus electrodes with polyacrylate binder to understand the formation of a solid electrolyte interphase (SEI) in alkyl carbonate ester and its evolution during cycling. The hard X-ray photoelectron spectroscopy (HAXPES) analysis suggests that SEI (passive film) consists of mainly inorganic species, which originate from decomposition of electrolyte solvents and additives. The thicker surface layer is formed during cycling in the additive-free electrol...

226 citations


Journal ArticleDOI
TL;DR: AeA1144 is the first known structure of this type among not only Fe-based superconductors but also other materials, which can be regarded as hybrid phases between AeFe 2As2 (Ae = Ca, Sr) and AFe2As2.
Abstract: Fe-based superconductors have attracted research interest because of their rich structural variety, which is due to their layered crystal structures. Here we report the new-structure-type Fe-based superconductors CaAFe4As4 (A = K, Rb, Cs) and SrAFe4As4 (A = Rb, Cs), which can be regarded as hybrid phases between AeFe2As2 (Ae = Ca, Sr) and AFe2As2. Unlike solid solutions such as (Ba1–xKx)Fe2As2 and (Sr1–xNax)Fe2As2, Ae and A do not occupy crystallographically equivalent sites because of the large differences between their ionic radii. Rather, the Ae and A layers are inserted alternately between the Fe2As2 layers in the c-axis direction in AeAFe4As4 (AeA1144). The ordering of the Ae and A layers causes a change in the space group from I4/mmm to P4/mmm, which is clearly apparent in powder X-ray diffraction patterns. AeA1144 is the first known structure of this type among not only Fe-based superconductors but also other materials. AeA1144 is formed as a line compound, and therefore, each AeA1144 has its own s...

217 citations


Journal ArticleDOI
TL;DR: In this article, the authors measured the redshift-space correlation function from a spectroscopic sample of 2783 emission line galaxies from the FastSound survey and obtained the first cosmological study at such high redshifts.
Abstract: We measure the redshift-space correlation function from a spectroscopic sample of 2783 emission line galaxies from the FastSound survey. The survey, which uses the Subaru Telescope and covers the redshift ranges of $1.19<$z$<1.55$, is the first cosmological study at such high redshifts. We detect clear anisotropy due to redshift-space distortions (RSD) both in the correlation function as a function of separations parallel and perpendicular to the line of sight and its quadrupole moment. RSD has been extensively used to test general relativity on cosmological scales at $z<1$. Adopting a LCDM cosmology with the fixed expansion history and no velocity dispersion $\sigma_{\rm v}=0$, and using the RSD measurements on scales above 8Mpc/h, we obtain the first constraint on the growth rate at the redshift, $f(z)\sigma_8(z)=0.482\pm 0.116$ at $z\sim 1.4$ after marginalizing over the galaxy bias parameter $b(z)\sigma_8(z)$. This corresponds to $4.2\sigma$ detection of RSD. Our constraint is consistent with the prediction of general relativity $f\sigma_8\sim 0.392$ within the $1-\sigma$ confidence level. When we allow $\sigma_{\rm v}$ to vary and marginalize it over, the growth rate constraint becomes $f\sigma_8=0.494^{+0.126}_{-0.120}$. We also demonstrate that by combining with the low-z constraints on $f\sigma_8$, high-z galaxy surveys like the FastSound can be useful to distinguish modified gravity models without relying on CMB anisotropy experiments.

Journal ArticleDOI
TL;DR: In this paper, a single-phase synthesis route for two polymorphs, namely distorted and undistorted P2-type Na2/3MnO2 having different Mn stoichiometry, was developed.
Abstract: To realize a reversible solid-state MnIII/IV redox couple in layered oxides, co-operative Jahn–Teller distortion (CJTD) of six-coordinate MnIII (t2g3–eg1) is a key factor in terms of structural and physical properties. We develop a single-phase synthesis route for two polymorphs, namely distorted and undistorted P2-type Na2/3MnO2 having different Mn stoichiometry, and investigate how the structural and stoichiometric difference influences electrochemical reaction. The distorted Na2/3MnO2 delivers 216 mAh g−1 as a 3 V class positive electrode, reaching 590 Wh (kg oxide)−1 with excellent cycle stability in a non-aqueous Na cell and demonstrates better electrochemical behavior compared to undistorted Na2/3MnO2. Furthermore, reversible phase transitions correlated with CJTD are found upon (de)sodiation for distorted Na2/3MnO2, providing a new insight into utilization of the MnIII/IV redox couple for positive electrodes of Na-ion batteries.

Journal ArticleDOI
TL;DR: Aun(SR)m has received significant attention as new functional nanomaterials because they exhibit size-specific physical and chemical properties that are not seen in bulk gold.

Journal ArticleDOI
TL;DR: The findings suggest that a combination of IDH, TERT, and MGMT refines the classification of grade II-IV diffuse gliomas, and patients with TERT mutant-MGMT unmethylated GBM have the poorest prognosis.
Abstract: The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients’ treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P < 0.0001). To investigate the association between TERT mutations and MGMT methylation on survival of patients with GBM, samples from a combined cohort of 453 IDH-wild-type GBM cases treated with radiation and temozolomide were analyzed. A multivariate Cox regression model revealed that the interaction between TERT and MGMT was significant for OS (P = 0.0064). Compared with TERT mutant-MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the interaction was the lowest in the TERT mutant-MGMT methylated GBM (HR, 0.266), followed by the TERT wild-type-MGMT methylated (HR, 0.317) and the TERT wild-type-MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant-MGMT unmethylated GBM have the poorest prognosis. Our findings suggest that a combination of IDH, TERT, and MGMT refines the classification of grade II-IV diffuse gliomas.

Journal ArticleDOI
TL;DR: In this article, the different types of optically active inorganic nanoparticles that are being used for optical bioimaging are reviewed in detail, and special attention is paid to fluorescent and inorganic persistent luminescence nanoparticles and how their different excitation mechanisms (no-photon, onephoton or multiphoton excited fluorescence) and working spectral ranges can be conveniently applied for in vitro and in vivo high contrast optical bio-imaging.
Abstract: The tremendous progress in the synthesis of different inorganic nanoparticles with pretailored size, shape, structural, compositional, and surface properties has significantly raised their potential applications in biomedicine. Optically active inorganic nanoparticles are those that, based on inorganic materials, can produce fluorescence or scattered light under suitable optical excitation. These outgoing radiations can be conveniently used for bioimaging purposes. In this work, the different types of optically active inorganic nanoparticles that are being used for optical bioimaging are reviewed in detail. Special attention is paid to fluorescent and inorganic persistent luminescence nanoparticles and how their different excitation mechanisms (no-photon, one-photon, or multiphoton excited fluorescence) and working spectral ranges can be conveniently applied for in vitro and in vivo high-contrast optical bioimaging.

Journal ArticleDOI
TL;DR: In this article, the authors demonstrate the detection of a single microwave photon propagating through a waveguide using an impedance-matched artificial Λ system comprising the dressed states of a driven superconducting qubit coupled to a microwave resonator.
Abstract: Single-photon detection is a requisite technique in quantum-optics experiments in both the optical and the microwave domains. However, the energy of microwave quanta are four to five orders of magnitude less than their optical counterpart, making the efficient detection of single microwave photons extremely challenging. Here we demonstrate the detection of a single microwave photon propagating through a waveguide. The detector is implemented with an impedance-matched artificial Λ system comprising the dressed states of a driven superconducting qubit coupled to a microwave resonator. Each signal photon deterministically induces a Raman transition in the Λ system and excites the qubit. The subsequent dispersive readout of the qubit produces a discrete ‘click’. We attain a high single-photon-detection efficiency of 0.66±0.06 with a low dark-count probability of 0.014±0.001 and a reset time of ∼400 ns. This detector can be exploited for various applications in quantum sensing, quantum communication and quantum information processing. Single-photon detection is challenging in the microwave regime due to the small photon energy. Here, the authors demonstrate the deterministic detection of single microwave photons through an impedenance-matched artificial Λ system composed by a driven superconducting qubit and a microwave resonator.

Journal ArticleDOI
TL;DR: A mechanistic link by which IL-17A modulates renal sodium transport is provided and it is suggested that IL- 17A inhibition may improve renal function in hypertension and other autoimmune disorders.
Abstract: Angiotensin II-induced hypertension is associated with an increase in T-cell production of interleukin-17A (IL-17A). Recently, we reported that IL-17A(-/-) mice exhibit blunted hypertension, preserved natriuresis in response to a saline challenge, and decreased renal sodium hydrogen exchanger 3 expression after 2 weeks of angiotensin II infusion compared with wild-type mice. In the current study, we performed renal transporter profiling in mice deficient in IL-17A or the related isoform, IL-17F, after 4 weeks of Ang II infusion, the time when the blood pressure reduction in IL-17A(-/-) mice is most prominent. Deficiency of IL-17A abolished the activation of distal tubule transporters, specifically the sodium-chloride cotransporter and the epithelial sodium channel and protected mice from glomerular and tubular injury. In human proximal tubule (HK-2) cells, IL-17A increased sodium hydrogen exchanger 3 expression through a serum and glucocorticoid-regulated kinase 1-dependent pathway. In mouse distal convoluted tubule cells, IL-17A increased sodium-chloride cotransporter activity in a serum and glucocorticoid-regulated kinase 1/Nedd4-2-dependent pathway. In both cell types, acute treatment with IL-17A induced phosphorylation of serum and glucocorticoid-regulated kinase 1 at serine 78, and treatment with a serum and glucocorticoid-regulated kinase 1 inhibitor blocked the effects of IL-17A on sodium hydrogen exchanger 3 and sodium-chloride cotransporter. Interestingly, both HK-2 and mouse distal convoluted tubule 15 cells produce endogenous IL-17A. IL17F had little or no effect on blood pressure or renal sodium transporter abundance. These studies provide a mechanistic link by which IL-17A modulates renal sodium transport and suggest that IL-17A inhibition may improve renal function in hypertension and other autoimmune disorders.

Journal ArticleDOI
TL;DR: In this paper, the cosmological implications of generalized Proca theories are investigated for both the background and the linear perturbation by taking into account the Lagrangian up to quintic order.
Abstract: We consider a massive vector field with derivative interactions that propagates only the 3 desired polarizations (besides two tensor polarizations from gravity) with second-order equations of motion in curved space-time. The cosmological implications of such generalized Proca theories are investigated for both the background and the linear perturbation by taking into account the Lagrangian up to quintic order. In the presence of a matter fluid with a temporal component of the vector field, we derive the background equations of motion and show the existence of de Sitter solutions relevant to the late-time cosmic acceleration. We also obtain conditions for the absence of ghosts and Laplacian instabilities of tensor, vector, and scalar perturbations in the small-scale limit. Our results are applied to concrete examples of the general functions in the theory, which encompass vector Galileons as a specific case. In such examples, we show that the de Sitter fixed point is always a stable attractor and study viable parameter spaces in which the no-ghost and stability conditions are satisfied during the cosmic expansion history.

Journal ArticleDOI
TL;DR: In this article, the authors consider higher-order derivative interactions beyond second-order generalized Proca theories that propagate only the three desired polarizations of a massive vector field besides the two tensor polarizations from gravity and show the existence of a constraint with a vanishing Hamiltonian that removes the would-be Ostrogradski ghost.

Journal ArticleDOI
TL;DR: In this article, the authors considered the finite interactions of the generalized Proca theory including the sixth-order Lagrangian and derived the full linear perturbation equations of motion on the flat Friedmann-Lemaitre-Robertson-Walker background in the presence of a matter perfect fluid.
Abstract: We consider the finite interactions of the generalized Proca theory including the sixth-order Lagrangian and derive the full linear perturbation equations of motion on the flat Friedmann-Lemaitre-Robertson-Walker background in the presence of a matter perfect fluid By construction, the propagating degrees of freedom (besides the matter perfect fluid) are two transverse vector perturbations, one longitudinal scalar, and two tensor polarizations The Lagrangians associated with intrinsic vector modes neither affect the background equations of motion nor the second-order action of tensor perturbations, but they do give rise to non-trivial modifications to the no-ghost condition of vector perturbations and to the propagation speeds of vector and scalar perturbations We derive the effective gravitational coupling $G_{\rm eff}$ with matter density perturbations under a quasi-static approximation on scales deep inside the sound horizon We find that the existence of intrinsic vector modes allows a possibility for reducing $G_{\rm eff}$ In fact, within the parameter space, $G_{\rm eff}$ can be even smaller than the Newton gravitational constant $G$ at the late cosmological epoch, with a peculiar phantom dark energy equation of state (without ghosts) The modifications to the slip parameter $\eta$ and the evolution of growth rate $f\sigma_8$ are discussed as well Thus, dark energy models in the framework of generalized Proca theories can be observationally distinguished from the $\Lambda$CDM model according to both cosmic growth and expansion history Furthermore, we study the evolution of vector perturbations and show that outside the vector sound horizon the perturbations are nearly frozen and start to decay with oscillations after the horizon entry

Journal ArticleDOI
TL;DR: It is demonstrated that CRTAM identifies CD4 T cells with cytotoxic function, and new insights into CD4+CTL development are presented.
Abstract: Naive T cells differentiate into various effector T cells, including CD4(+) helper T cell subsets and CD8(+) cytotoxic T cells (CTL). Although cytotoxic CD4(+) T cells (CD4 +: CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4(+) T cells that express class I-restricted T cell-associated molecule (CRTAM) upon activation possesses the characteristics of both CD4(+) and CD8(+) T cells. CRTAM(+) CD4(+) T cells secrete IFN-γ, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM(+) T cells are the precursor of CD4(+)CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-γ, expression of CTL-related genes, and cytotoxic activity. The induction of CD4(+)CTL and IFN-γ production requires CRTAM-mediated intracellular signaling. CRTAM(+) T cells traffic to mucosal tissues and inflammatory sites and developed into CD4(+)CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-γ secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4(+)CTL through the induction of Eomes and CTL-related gene.

Journal ArticleDOI
TL;DR: B cell–intrinsic IFN-γ receptor signaling through STAT1 is required for the generation of spontaneous germinal centers, which can lead to pathogenic autoantibody production.
Abstract: Spontaneously developed germinal centers (GCs [Spt-GCs]) harbor autoreactive B cells that generate somatically mutated and class-switched pathogenic autoantibodies (auto-Abs) to promote autoimmunity. However, the mechanisms that regulate Spt-GC development are not clear. In this study, we report that B cell-intrinsic IFN-γ receptor (IFN-γR) and STAT1 signaling are required for Spt-GC and follicular T helper cell (Tfh cell) development. We further demonstrate that IFN-γR and STAT1 signaling control Spt-GC and Tfh cell formation by driving T-bet expression and IFN-γ production by B cells. Global or B cell-specific IFN-γR deficiency in autoimmune B6.Sle1b mice leads to significantly reduced Spt-GC and Tfh cell responses, resulting in diminished antinuclear Ab reactivity and IgG2c and IgG2b auto-Ab titers compared with B6.Sle1b mice. Additionally, we observed that the proliferation and differentiation of DNA-reactive B cells into a GC B cell phenotype require B cell-intrinsic IFN-γR signaling, suggesting that IFN-γR signaling regulates GC B cell tolerance to nuclear self-antigens. The IFN-γR deficiency, however, does not affect GC, Tfh cell, or Ab responses against T cell-dependent foreign antigens, indicating that IFN-γR signaling regulates autoimmune, but not the foreign antigen-driven, GC and Tfh cell responses. Together, our data define a novel B cell-intrinsic IFN-γR signaling pathway specific to Spt-GC development and autoimmunity. This novel pathway can be targeted for future pharmacological intervention to treat systemic lupus erythematosus.

Journal ArticleDOI
01 Nov 2016
TL;DR: In this article, a cyclic alkylene carbonate based solution containing a NaClO4 or NaPF6 salt with a fluoroethylene carbonate (FEC) additive was examined to study electrolyte dependency for sodium-ion batteries.
Abstract: Electrochemical sodium insertion for hard carbon is examined in a cyclic alkylene carbonate based solution containing a NaClO4 or NaPF6 salt with a fluoroethylene carbonate (FEC) additive to study electrolyte dependency for sodium-ion batteries. NaPF6-based electrolytes provide superior reversibility and cyclability of sodium insertion into hard carbon compared with NaClO4-based ones. The FEC-derived passivation film improves capacity retention because of better passivation with a thinner surface layer, as revealed by hard and soft X-ray photoelectron spectroscopy (PES). The use of both the NaPF6 salt and FEC additive results in a synergetic effect on passivation for the hard-carbon electrode, leading to enhanced cycle performance. Hard-carbon electrodes with polyvinylidene difluoride binder in propylene carbonate based electrolytes containing NaPF6 and FEC demonstrate excellent capacity retention with a reversible capacity of about 250 mAh g−1. The difference in capacity retention for the electrolytes is expected to originate as a consequence of the difference in the surface interphase layer formed on the hard-carbon electrodes. Surface analyses with PES and time-of-flight secondary ion mass spectrometry reveal differences in surface and passivation chemistry which depend on the salts, solvents, and FEC additives used for the hard-carbon negative electrodes.

Journal ArticleDOI
TL;DR: The hierarchy in the bond stiffness in thiolate-protected, icosahedral-based gold clusters Au25( SC2H4Ph)18, Au38(SC2H 4Ph)24 and Au144(SC 2H4 Ph)60 is elucidated by analysing Au L3-edge extended X-ray absorption fine structure data.
Abstract: Unique thermal properties of metal clusters are believed to originate from the hierarchy of the bonding. However, an atomic-level understanding of how the bond stiffnesses are affected by the atomic packing of a metal cluster and the interfacial structure with the surrounding environment has not been attained to date. Here we elucidate the hierarchy in the bond stiffness in thiolate-protected, icosahedral-based gold clusters Au25(SC2H4Ph)18, Au38(SC2H4Ph)24 and Au144(SC2H4Ph)60 by analysing Au L3-edge extended X-ray absorption fine structure data. The Au-Au bonds have different stiffnesses depending on their lengths. The long Au-Au bonds, which are more flexible than those in the bulk metal, are located at the icosahedral-based gold core surface. The short Au-Au bonds, which are stiffer than those in the bulk metal, are mainly distributed along the radial direction and form a cyclic structural backbone with the rigid Au-SR oligomers.

Journal ArticleDOI
TL;DR: In this paper, a solid solution of NaFeO2-NaCoO2 is synthesized and the mechanisms behind their excellent electrochemical performance are studied in comparison to those of their respective end-members.
Abstract: Na-ion batteries have become promising candidates for large-scale energy-storage systems because of the abundant Na resources and they have attracted considerable academic interest because of their unique behavior, such as their electrochemical activity for the Fe3+/Fe4+ redox couple. The high-rate performance derived from the low Lewis-acidity of the Na+ ions is another advantage of Na-ion batteries and has been demonstrated in NaFe1/2Co1/2O2 solutions. Here, a solid solution of NaFeO2-NaCoO2 is synthesized and the mechanisms behind their excellent electrochemical performance are studied in comparison to those of their respective end-members. The combined analysis of operando X-ray diffraction, ex situ X-ray absorption spectroscopy, and density functional theory (DFT) calculations for Na1– x Fe1/2Co1/2O2 reveals that the O3-type phase transforms into a P3-type phase coupled with Na+/vacancy ordering, which has not been observed in O3-type NaFeO2. The substitution of Co for Fe stabilizes the P3-type phase formed by sodium extraction and could suppress the irreversible structural change that is usually observed in O3-type NaFeO2, resulting in a better cycle retention and higher rate performance. Although no ordering of the transition metal ions is seen in the neutron diffraction experiments, as supported by Monte-Carlo simulations, the formation of a superlattice originating from the Na+/vacancy ordering is found by synchrotron X-ray diffraction for Na0.5Fe1/2Co1/2O2, which may involve a potential step in the charge/discharge profiles.

Journal ArticleDOI
TL;DR: Feeding at an unusual time of day (inactive phase) desynchronizes peripheral clocks and causes obesity and metabolic disorders by inducing leptin resistance, hyperphagia, physical inactivity, hepatic fat accumulation and adiposity.
Abstract: Background The circadian clock regulates various physiological and behavioral rhythms such as feeding and locomotor activity. Feeding at unusual times of the day (inactive phase) is thought to be associated with obesity and metabolic disorders in experimental animals and in humans. Objective The present study aimed to determine the underlying mechanisms through which time-of-day-dependent feeding influences metabolic homeostasis. Methods We compared food consumption, wheel-running activity, core body temperature, hormonal and metabolic variables in blood, lipid accumulation in the liver, circadian expression of clock and metabolic genes in peripheral tissues, and body weight gain between mice fed only during the sleep phase (DF, daytime feeding) and those fed only during the active phase (NF, nighttime feeding). All mice were fed with the same high-fat high-sucrose diet throughout the experiment. To the best of our knowledge, this is the first study to examine the metabolic effects of time-imposed restricted feeding (RF) in mice with free access to a running wheel. Results After one week of RF, DF mice gained more weight and developed hyperphagia, higher feed efficiency and more adiposity than NF mice. The daily amount of running on the wheel was rapidly and obviously reduced by DF, which might have been the result of time-of-day-dependent hypothermia. The amount of daily food consumption and hypothalamic mRNA expression of orexigenic neuropeptide Y and agouti-related protein were significantly higher in DF, than in NF mice, although levels of plasma leptin that fluctuate in an RF-dependent circadian manner, were significantly higher in DF mice. These findings suggested that the DF induced leptin resistance. The circadian phases of plasma insulin and ghrelin were synchronized to RF, although the corticosterone phase was unaffected. Peak levels of plasma insulin were remarkably higher in DF mice, although HOMA-IR was identical between the two groups. Significantly more free fatty acids, triglycerides and cholesterol accumulated in the livers of DF, than NF mice, which resulted from the increased expression of lipogenic genes such as Scd1, Acaca, and Fasn. Temporal expression of circadian clock genes became synchronized to RF in the liver but not in skeletal muscle, suggesting that uncoupling metabolic rhythms between the liver and skeletal muscle also contribute to DF-induced adiposity. Conclusion Feeding at an unusual time of day (inactive phase) desynchronizes peripheral clocks and causes obesity and metabolic disorders by inducing leptin resistance, hyperphagia, physical inactivity, hepatic fat accumulation and adiposity.

Journal ArticleDOI
TL;DR: A critical role is revealed for IL-1β produced by a TH17 cell–intrinsic ASC–NLRP3–caspase-8 inflammasome during inflammation of the central nervous system.
Abstract: Interleukin 1β (IL-1β) is critical for the in vivo survival, expansion and effector function of IL-17-producing helper T (T(H)17) cells during autoimmune responses, including experimental autoimmune encephalomyelitis (EAE). However, the spatiotemporal role and cellular source of IL-1β during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell-intrinsic inflammasome that drives IL-1β production during T(H)17-mediated EAE pathogenesis. Activation of T cell antigen receptors induced expression of pro-IL-1β, whereas ATP stimulation triggered T cell production of IL-1β via ASC-NLRP3-dependent caspase-8 activation. IL-1R was detected on T(H)17 cells but not on type 1 helper T (T(H)1) cells, and ATP-treated T(H)17 cells showed enhanced survival compared with ATP-treated T(H)1 cells, suggesting autocrine action of T(H)17-derived IL-1β. Together these data reveal a critical role for IL-1β produced by a T(H)17 cell-intrinsic ASC-NLRP3-caspase-8 inflammasome during inflammation of the central nervous system.

Journal ArticleDOI
TL;DR: In this paper, the authors demonstrate optical driving at a petahertz frequency in the wide-bandgap semiconductor gallium nitride, which corresponds to instantaneous light-induced switching from insulator to conductor.
Abstract: Experiments showing that electron dynamics can be controlled on attosecond timescales suggest that wide-bandgap semiconductors could be exploited for petahertz signal processing technologies. High-speed photonic and electronic devices at present rely on radiofrequency electric fields to control the physical properties of a semiconductor1, which limits their operating speed to terahertz frequencies (1012 Hz; ref. 2). Using the electric field from intense light pulses, however, could extend the operating frequency into the petahertz regime (1015 Hz; ref. 3). Here we demonstrate optical driving at a petahertz frequency in the wide-bandgap semiconductor gallium nitride. Few-cycle near-infrared pulses are shown to induce electric interband polarization though a multiphoton process. Dipole oscillations with a periodicity of 860 as are revealed in the gallium nitride electron and hole system by using the quantum interference between the two transitions from the valence and conduction band states, which are probed by an extremely short isolated attosecond pulse with a coherent broadband spectrum. In principle, this shows that the conductivity of the semiconductor can be manipulated on attosecond timescales, which corresponds to instantaneous light-induced switching from insulator to conductor. The resultant dipole frequency reaches 1.16 PHz, showing the potential for future high-speed signal processing technologies based on wide-bandgap semiconductors.

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TL;DR: Using site-selective nuclear magnetic resonance, a non-uniform cone reshaping accompanied by a bandwidth reduction and an emergent ferrimagnetism in tilted Dirac cones that appear on the verge of charge ordering in an organic compound is found.
Abstract: The Coulomb interaction among massless Dirac fermions in graphene is unscreened around the isotropic Dirac points, causing a logarithmic velocity renormalization and a cone reshaping. In less symmetric Dirac materials possessing anisotropic cones with tilted axes, the Coulomb interaction can provide still more exotic phenomena, which have not been experimentally unveiled yet. Here, using site-selective nuclear magnetic resonance, we find a non-uniform cone reshaping accompanied by a bandwidth reduction and an emergent ferrimagnetism in tilted Dirac cones that appear on the verge of charge ordering in an organic compound. Our theoretical analyses based on the renormalization-group approach and the Hubbard model show that these observations are the direct consequences of the long-range and short-range parts of the Coulomb interaction, respectively. The cone reshaping and the bandwidth renormalization, as well as the magnetic behaviour revealed here, can be ubiquitous and vital for many Dirac materials.

Journal ArticleDOI
20 Dec 2016-eLife
TL;DR: It is reported that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal Ccr5 overexpression caused memory deficits, and indicates that C CR5 has a role in the cognitive deficits caused by HIV.
Abstract: Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.