Showing papers by "Nagoya University published in 2016"

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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.

Supramolecular Helical Systems: Helical Assemblies of Small Molecules, Foldamers, and Polymers with Chiral Amplification and Their Functions

Abstract: In this review, we describe the recent advances in supramolecular helical assemblies formed from chiral and achiral small molecules, oligomers (foldamers), and helical and nonhelical polymers from the viewpoints of their formations with unique chiral phenomena, such as amplification of chirality during the dynamic helically assembled processes, properties, and specific functionalities, some of which have not been observed in or achieved by biological systems. In addition, a brief historical overview of the helical assemblies of small molecules and remarkable progress in the synthesis of single-stranded and multistranded helical foldamers and polymers, their properties, structures, and functions, mainly since 2009, will also be described.

Genome evolution in the allotetraploid frog Xenopus laevis

Abstract: To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.

Global change pressures on soils from land use and management.

Abstract: Soils are subject to varying degrees of direct or indirect human disturbance, constituting a major global change driver. Factoring out natural from direct and indirect human influence is not always straightforward, but some human activities have clear impacts. These include land-use change, land management and land degradation (erosion, compaction, sealing and salinization). The intensity of land use also exerts a great impact on soils, and soils are also subject to indirect impacts arising from human activity, such as acid deposition (sulphur and nitrogen) and heavy metal pollution. In this critical review, we report the state-of-the-art understanding of these global change pressures on soils, identify knowledge gaps and research challenges and highlight actions and policies to minimize adverse environmental impacts arising from these global change drivers. Soils are central to considerations of what constitutes sustainable intensification. Therefore, ensuring that vulnerable and high environmental value soils are considered when protecting important habitats and ecosystems, will help to reduce the pressure on land from global change drivers. To ensure that soils are protected as part of wider environmental efforts, a global soil resilience programme should be considered, to monitor, recover or sustain soil fertility and function, and to enhance the ecosystem services provided by soils. Soils cannot, and should not, be considered in isolation of the ecosystems that they underpin and vice versa. The role of soils in supporting ecosystems and natural capital needs greater recognition. The lasting legacy of the International Year of Soils in 2015 should be to put soils at the centre of policy supporting environmental protection and sustainable development.

The quiescent intracluster medium in the core of the Perseus cluster

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.

FERMI-LAT OBSERVATIONS of HIGH-ENERGY γ-RAY EMISSION TOWARD the GALACTIC CENTER

Abstract: The Fermi Large Area Telescope (LAT) has provided the most detailed view to date of the emission toward the Galactic center (GC) in high-energy gamma-rays. This paper describes the analysis of data ...

Muon reconstruction performance of the ATLAS detector in proton–proton collision data at √ s =13 TeV

Abstract: This article documents the performance of the ATLAS muon identification and reconstruction using the first LHC dataset recorded at s√ = 13 TeV in 2015. Using a large sample of J/ψ→μμ and Z→μμ decays from 3.2 fb−1 of pp collision data, measurements of the reconstruction efficiency, as well as of the momentum scale and resolution, are presented and compared to Monte Carlo simulations. The reconstruction efficiency is measured to be close to 99% over most of the covered phase space (|η| 2.2, the pT resolution for muons from Z→μμ decays is 2.9% while the precision of the momentum scale for low-pT muons from J/ψ→μμ decays is about 0.2%.

DEVELOPMENT of the MODEL of GALACTIC INTERSTELLAR EMISSION for STANDARD POINT-SOURCE ANALYSIS of FERMI LARGE AREA TELESCOPE DATA

Abstract: Most of the celestial γ rays detected by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope originate from the interstellar medium when energetic cosmic rays interact with interstellar nucleons and photons. Conventional point-source and extended-source studies rely on the modeling of this diffuse emission for accurate characterization. Here, we describe the development of the Galactic Interstellar Emission Model (GIEM), which is the standard adopted by the LAT Collaboration and is publicly available. This model is based on a linear combination of maps for interstellar gas column density in Galactocentric annuli and for the inverse-Compton emission produced in the Galaxy. In the GIEM, we also include large-scale structures like Loop I and the Fermi bubbles. The measured gas emissivity spectra confirm that the cosmic-ray proton density decreases with Galactocentric distance beyond 5 kpc from the Galactic Center. The measurements also suggest a softening of the proton spectrum with Galactocentric distance. We observe that the Fermi bubbles have boundaries with a shape similar to a catenary at latitudes below 20° and we observe an enhanced emission toward their base extending in the north and south Galactic directions and located within ∼4° of the Galactic Center.

Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice

Abstract: A genome-wide association study (GWAS) can be a powerful tool for the identification of genes associated with agronomic traits in crop species, but it is often hindered by population structure and the large extent of linkage disequilibrium. In this study, we identified agronomically important genes in rice using GWAS based on whole-genome sequencing, followed by the screening of candidate genes based on the estimated effect of nucleotide polymorphisms. Using this approach, we identified four new genes associated with agronomic traits. Some genes were undetectable by standard SNP analysis, but we detected them using gene-based association analysis. This study provides fundamental insights relevant to the rapid identification of genes associated with agronomic traits using GWAS and will accelerate future efforts aimed at crop improvement.

Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease

Abstract: Obesity is causally linked with the development of cardiovascular disorders. Accumulating evidence indicates that cardiovascular disease is the collateral damage of obesity-driven adipose tissue dysfunction that promotes a chronic inflammatory state within the organism. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. The microenvironment of adipose tissue will affect the adipokine secretome, having actions on remote tissues. Obesity typically leads to the upregulation of proinflammatory adipokines and the downregulation of anti-inflammatory adipokines, thereby contributing to the pathogenesis of cardiovascular diseases. In this review, we focus on the microenvironment of adipose tissue and how it influences cardiovascular disorders, including atherosclerosis and ischemic heart diseases, through the systemic actions of adipokines.

Catalytic Methods for Aromatic C–H Amination: An Ideal Strategy for Nitrogen-Based Functional Molecules

Abstract: Transformations of aromatic compounds into the corresponding amines, amides, and imides through carbon–hydrogen (C–H) bond functionalization represent one of the most step- and atom-economical methods for the synthesis of arylamine compounds. Because arylamines are privileged structures in materials- and biology-oriented functional molecules, the development of novel and efficient synthetic methods for aromatic C–H amination has received significant attention from a wide range of research fields including materials and pharmaceuticals. This review covers recent advances in catalytic aromatic C–H amination reactions. An array of recently developed new reactions are categorized by the nature of aromatic substrates: (1) 5-membered heteroarenes, (2) arenes having a nitrogen moiety in the molecule (intramolecular C–H amination), (3) arenes having a directing group, (4) simple arenes with excess amounts, and (5) simple arenes as the limiting reagents.

Roles of regulatory T cells in cancer immunity.

Abstract: CD4(+) regulatory T cells (Tregs) expressing the transcription factor FoxP3 are highly immune suppressive and play central roles in the maintenance of self-tolerance and immune homeostasis, yet in malignant tumors they promote tumor progression by suppressing effective antitumor immunity. Indeed, higher infiltration by Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models. Additionally, increased numbers of Tregs and, in particular, decreased ratios of CD8(+) T cells to Tregs among tumor-infiltrating lymphocytes are correlated with poor prognosis in various types of human cancers. The recent success of cancer immunotherapy represented by immune checkpoint blockade has provided a new insight in cancer treatment, yet more than half of the treated patients did not experience clinical benefits. Identifying biomarkers that predict clinical responses and developing novel immunotherapies are therefore urgently required. Cancer patients whose tumors contain a large number of neoantigens stemming from gene mutations, which have not been previously recognized by the immune system, provoke strong antitumor T-cell responses associated with clinical responses following immune checkpoint blockade, depending on the resistance to Treg-mediated suppression. Thus, integration of a strategy restricting Treg-mediated immune suppression may expand the therapeutic spectrum of cancer immunotherapy towards patients with a lower number of neoantigens. In this review, we address the current understanding of Treg-mediated immune suppressive mechanisms in cancer, the involvement of Tregs in cancer immunotherapy, and strategies for effective and tolerable Treg-targeted therapy.

Performance of $b$-Jet Identification in the ATLAS Experiment

Abstract: The identification of jets containing b hadrons is important for the physics programme of the ATLAS experiment at the Large Hadron Collider. Several algorithms to identify jets containing b hadrons are described, ranging from those based on the reconstruction of an inclusive secondary vertex or the presence of tracks with large impact parameters to combined tagging algorithms making use of multi-variate discriminants. An independent b-tagging algorithm based on the reconstruction of muons inside jets as well as the b-tagging algorithm used in the online trigger are also presented. The b-jet tagging efficiency, the c-jet tagging efficiency and the mistag rate for light flavour jets in data have been measured with a number of complementary methods. The calibration results are presented as scale factors defined as the ratio of the efficiency (or mistag rate) in data to that in simulation. In the case of b jets, where more than one calibration method exists, the results from the various analyses have been combined taking into account the statistical correlation as well as the correlation of the sources of systematic uncertainty.

Structurally uniform and atomically precise carbon nanostructures

Abstract: Nanometre-sized carbon materials consisting of benzene units oriented in unique geometric patterns, hereafter named nanocarbons, conduct electricity, absorb and emit light, and exhibit interesting magnetic properties. Spherical fullerene C60, cylindrical carbon nanotubes and sheet-like graphene are representative forms of nanocarbons, and theoretical simulations have predicted several exotic 3D nanocarbon structures. At present, synthetic routes to nanocarbons mainly lead to mixtures of molecules with a range of different structures and properties, which cannot be easily separated or refined into pure forms. Some researchers believe that it is impossible to synthesize these materials in a precise manner. Obtaining ‘pure’ nanocarbons is a great challenge in the field of nanocarbon science, and the construction of structurally uniform nanocarbons, ideally as single molecules, is crucial for the development of functional materials in nanotechnology, electronics, optics and biomedical applications. This Review highlights the organic chemistry approach — more specifically, bottom-up construction with atomic precision — that is currently the most promising strategy towards this end. Conventional synthesis of nanocarbons, such as graphene, fullerenes and carbon nanotubes, yields mixtures of molecules with varying structures. However, harnessing the full potential of these materials demands atomically precise synthesis methods. Recent advances using organic chemistry are discussed in this Review.

Geomorphic and geologic controls of geohazards induced by Nepal’s 2015 Gorkha earthquake

Abstract: The Gorkha earthquake (M 7.8) on 25 April 2015 and later aftershocks struck South Asia, killing ~9,000 and damaging a large region. Supported by a large campaign of responsive satellite data acquisitions over the earthquake disaster zone, our team undertook a satellite image survey of the earthquakes’ induced geohazards in Nepal and China and an assessment of the geomorphic, tectonic, and lithologic controls on quake-induced landslides. Timely analysis and communication aided response and recovery and informed decision makers. We mapped 4,312 co-seismic and post-seismic landslides. We also surveyed 491 glacier lakes for earthquake damage, but found only 9 landslide-impacted lakes and no visible satellite evidence of outbursts. Landslide densities correlate with slope, peak ground acceleration, surface downdrop, and specific metamorphic lithologies and large plutonic intrusions.

SINTERING-INDUCED DUST RING FORMATION in PROTOPLANETARY DISKS: APPLICATION to the HL TAU DISK

Abstract: The latest observation of HL Tau by ALMA revealed spectacular concentric dust rings in its circumstellar disk. We attempt to explain the multiple ring structure as a consequence of aggregate sintering. Sintering is known to reduce the sticking efficiency of dust aggregates and occurs at temperatures slightly below the sublimation point of their constituent material. We here present a dust growth model incorporating sintering and use it to simulate global dust evolution due to sintering, coagulation, fragmentation, and radial inward drift in a modeled HL Tau disk. We show that aggregates consisting of multiple species of volatile ices experience sintering, collisionally disrupt, and pile up at multiple locations slightly outside the snow lines of the volatiles. At wavelengths of 0.87--1.3 mm, these sintering zones appear as bright, optically thick rings with a spectral slope of $\approx 2$, whereas the non-sintering zones as darker, optically thinner rings of a spectral slope of $\approx$ 2.3--2.5. The observational features of the sintering and non-sintering zones are consistent with those of the major bright and dark rings found in the HL Tau disk, respectively. Radial pileup and vertical settling occur simultaneously if disk turbulence is weak and if monomers constituting the aggregates are $\sim 1~{\rm \mu m}$ in radius. For the radial gas temperature profile of $T = 310(r/1~{\rm AU})^{-0.57}~{\rm K}$, our model perfectly reproduces the brightness temperatures of the optically thick bright rings, and reproduces their orbital distances to an accuracy of $\lesssim$ 30%.

Diamond family of nanoparticle superlattices

Abstract: Diamond lattices formed by atomic or colloidal elements exhibit remarkable functional properties. However, building such structures via self-assembly has proven to be challenging because of the low packing fraction, sensitivity to bond orientation, and local heterogeneity. We report a strategy for creating a diamond superlattice of nano-objects via self-assembly and demonstrate its experimental realization by assembling two variant diamond lattices, one with and one without atomic analogs. Our approach relies on the association between anisotropic particles with well-defined tetravalent binding topology and isotropic particles. The constrained packing of triangular binding footprints of truncated tetrahedra on a sphere defines a unique three-dimensional lattice. Hence, the diamond self-assembly problem is solved via its mapping onto two-dimensional triangular packing on the surface of isotropic spherical particles.

2D coherent charge transport in highly ordered conducting polymers doped by solid state diffusion

Abstract: Doping is one of the most important methods to control charge carrier concentration in semiconductors. Ideally, the introduction of dopants should not perturb the ordered microstructure of the semiconducting host. In some systems, such as modulation-doped inorganic semiconductors or molecular charge transfer crystals, this can be achieved by spatially separating the dopants from the charge transport pathways. However, in conducting polymers, dopants tend to be randomly distributed within the conjugated polymer, and as a result the transport properties are strongly affected by the resulting structural and electronic disorder. Here, we show that in the highly ordered lamellar microstructure of a regioregular thiophene-based conjugated polymer, a small-molecule p-type dopant can be incorporated by solid state diffusion into the layers of solubilizing side chains without disrupting the conjugated layers. In contrast to more disordered systems, this allows us to observe coherent, free-electron-like charge transport properties, including a nearly ideal Hall effect in a wide temperature range, a positive magnetoconductance due to weak localization and the Pauli paramagnetic spin susceptibility.

Performance of pile-up mitigation techniques for jets in pp collisions at √s = 8 TeV using the ATLAS detector

Abstract: The large rate of multiple simultaneous protonproton interactions, or pile-up, generated by the Large Hadron Collider in Run 1 required the development of many new techniques to mitigate the advers ...

An Adsorbate Discriminatory Gate Effect in a Flexible Porous Coordination Polymer for Selective Adsorption of CO2 over C2H2

Abstract: The adsorptive separation of C2H2 and CO2 via porous materials is nontrivial due to the close similarities of their boiling points and kinetic diameters. In this work, we describe a new flexible porous coordination polymer (PCP) [Mn(bdc)(dpe)] (H2bdc = 1,4-benzenedicarboxylic acid, dpe = 1,2-di(4-pyridyl)ethylene) having zero-dimensional pores, which shows an adsorbate discriminatory gate effect. The compound shows gate opening type abrupt adsorption for C2H2 but not for CO2, leading to an appreciable selective adsorption of CO2 over C2H2 at near ambient temperature (273 K). The origin of this unique selectivity, as unveiled by in situ adsorption-X-ray diffraction experiments and density functional theory calculations, is due to vastly different orientations between the phenylene ring of bdc and each gas in the nanopores. The structural change by photochemical transformation of this PCP via [2 + 2] photodimerization leads to the removal of inverse CO2/C2H2 selectivity, verifying the mechanism of the guest discriminatory gate effect.

Consensus Paper: Cerebellar Development.

Abstract: The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

2FHL: The Second Catalog of Hard Fermi-LAT Sources

Abstract: We present a catalog of sources detected above 50 GeV by the Fermi-Large Area Telescope (LAT) in 80 months of data. The newly delivered Pass 8 event-level analysis allows the detection and characterization of sources in the 50 GeV–2 TeV energy range. In this energy band, Fermi-LAT has detected 360 sources, which constitute the second catalog of hard Fermi-LAT sources (2FHL). The improved angular resolution enables the precise localization of point sources (~1farcm7 radius at 68% C. L.) and the detection and characterization of spatially extended sources. We find that 86% of the sources can be associated with counterparts at other wavelengths, of which the majority (75%) are active galactic nuclei and the rest (11%) are Galactic sources. Only 25% of the 2FHL sources have been previously detected by Cherenkov telescopes, implying that the 2FHL provides a reservoir of candidates to be followed up at very high energies. This work closes the energy gap between the observations performed at GeV energies by Fermi-LAT on orbit and the observations performed at higher energies by Cherenkov telescopes from the ground.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Abstract: Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Localization and broadband follow-up of the gravitational-wave transient GW150914

Abstract: A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams.

Luminosity determination in pp collisions at √s = 8 TeV using the ATLAS detector at the LHC

Abstract: The luminosity determination for the ATLAS detector at the LHC during pp collisions at s√= 8 TeV in 2012 is presented. The evaluation of the luminosity scale is performed using several luminometers ...