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Showing papers by "Kyoto University published in 2013"


Journal ArticleDOI
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.

2,831 citations


Proceedings Article
Marco Cuturi1
05 Dec 2013
TL;DR: This work smooths the classic optimal transport problem with an entropic regularization term, and shows that the resulting optimum is also a distance which can be computed through Sinkhorn's matrix scaling algorithm at a speed that is several orders of magnitude faster than that of transport solvers.
Abstract: Optimal transport distances are a fundamental family of distances for probability measures and histograms of features. Despite their appealing theoretical properties, excellent performance in retrieval tasks and intuitive formulation, their computation involves the resolution of a linear program whose cost can quickly become prohibitive whenever the size of the support of these measures or the histograms' dimension exceeds a few hundred. We propose in this work a new family of optimal transport distances that look at transport problems from a maximum-entropy perspective. We smooth the classic optimal transport problem with an entropic regularization term, and show that the resulting optimum is also a distance which can be computed through Sinkhorn's matrix scaling algorithm at a speed that is several orders of magnitude faster than that of transport solvers. We also show that this regularized distance improves upon classic optimal transport distances on the MNIST classification problem.

2,681 citations


Journal ArticleDOI
TL;DR: The tunability of the photoluminescence (PL) properties of monolayer (1L)-MoS2 is demonstrated via chemical doping and enables convenient control of optical and electrical properties of atomically thin MoS2.
Abstract: We demonstrate the tunability of the photoluminescence (PL) properties of monolayer (1L)-MoS2 via chemical doping. The PL intensity of 1L-MoS2 was drastically enhanced by the adsorption of p-type dopants with high electron affinity but reduced by the adsorption of n-type dopants. This PL modulation results from switching between exciton PL and trion PL depending on carrier density in 1L-MoS2. Achievement of the extraction and injection of carriers in 1L-MoS2 by this solution-based chemical doping method enables convenient control of optical and electrical properties of atomically thin MoS2.

1,210 citations


Journal ArticleDOI
TL;DR: The discovery of novel biomarkers that are able to predict the clinical response to pro-oxidant therapies is a crucial challenge to overcome to allow for the personalization of cancer therapies.

1,110 citations


Journal ArticleDOI
18 Jan 2013-Science
TL;DR: With the first plenary meeting of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) soon under way, partners are developing—and seeking consensus around—Essential Biod diversity Variables (EBVs) that could form the basis of monitoring programs worldwide.
Abstract: Reducing the rate of biodiversity loss and averting dangerous biodiversity change are international goals, reasserted by the Aichi Targets for 2020 by Parties to the United Nations (UN) Convention on Biological Diversity (CBD) after failure to meet the 2010 target (1, 2). However, there is no global, harmonized observation system for delivering regular, timely data on biodiversity change (3). With the first plenary meeting of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) soon under way, partners from the Group on Earth Observations Biodiversity Observation Network (GEO BON) (4) are developing—and seeking consensus around—Essential Biodiversity Variables (EBVs) that could form the basis of monitoring programs worldwide.

1,074 citations


Journal ArticleDOI
14 Mar 2013-Nature
TL;DR: It is suggested that osterix-expressing stromal cells comprise a distinct niche that supports B-lymphoid progenitors and retains HPCs in the bone marrow, and that expression of CXCL12 from stroma cells in the perivascular region, including endothelial cells and mesenchymal progenitor, supports HSCs.
Abstract: Haematopoietic stem cells (HSCs) primarily reside in the bone marrow where signals generated by stromal cells regulate their self-renewal, proliferation and trafficking. Endosteal osteoblasts and perivascular stromal cells including endothelial cells, CXCL12-abundant reticular cells, leptin-receptor-positive stromal cells, and nestin-green fluorescent protein (GFP)-positive mesenchymal progenitors have all been implicated in HSC maintenance. However, it is unclear whether specific haematopoietic progenitor cell (HPC) subsets reside in distinct niches defined by the surrounding stromal cells and the regulatory molecules they produce. CXCL12 (chemokine (C-X-C motif) ligand 12) regulates both HSCs and lymphoid progenitors and is expressed by all of these stromal cell populations. Here we selectively deleted Cxcl12 from candidate niche stromal cell populations and characterized the effect on HPCs. Deletion of Cxcl12 from mineralizing osteoblasts has no effect on HSCs or lymphoid progenitors. Deletion of Cxcl12 from osterix-expressing stromal cells, which include CXCL12-abundant reticular cells and osteoblasts, results in constitutive HPC mobilization and a loss of B-lymphoid progenitors, but HSC function is normal. Cxcl12 deletion from endothelial cells results in a modest loss of long-term repopulating activity. Strikingly, deletion of Cxcl12 from nestin-negative mesenchymal progenitors using Prx1-cre (Prx1 also known as Prrx1) is associated with a marked loss of HSCs, long-term repopulating activity, HSC quiescence and common lymphoid progenitors. These data suggest that osterix-expressing stromal cells comprise a distinct niche that supports B-lymphoid progenitors and retains HPCs in the bone marrow, and that expression of CXCL12 from stromal cells in the perivascular region, including endothelial cells and mesenchymal progenitors, supports HSCs.

1,069 citations


Proceedings ArticleDOI
23 Jun 2013
TL;DR: This paper regards saliency map computation as a regression problem, which is based on multi-level image segmentation, and uses the supervised learning approach to map the regional feature vector to a saliency score, and finally fuses the saliency scores across multiple levels, yielding the salency map.
Abstract: Salient object detection has been attracting a lot of interest, and recently various heuristic computational models have been designed. In this paper, we regard saliency map computation as a regression problem. Our method, which is based on multi-level image segmentation, uses the supervised learning approach to map the regional feature vector to a saliency score, and finally fuses the saliency scores across multiple levels, yielding the saliency map. The contributions lie in two-fold. One is that we show our approach, which integrates the regional contrast, regional property and regional background ness descriptors together to form the master saliency map, is able to produce superior saliency maps to existing algorithms most of which combine saliency maps heuristically computed from different types of features. The other is that we introduce a new regional feature vector, background ness, to characterize the background, which can be regarded as a counterpart of the objectness descriptor [2]. The performance evaluation on several popular benchmark data sets validates that our approach outperforms existing state-of-the-arts.

1,057 citations


Journal ArticleDOI
TL;DR: It is demonstrated that G PR43-deficient mice are obese on a normal diet, whereas mice overexpressing GPR43 specifically in adipose tissue remain lean even when fed a high-fat diet.
Abstract: The gut microbiota affects nutrient acquisition and energy regulation of the host, and can influence the development of obesity, insulin resistance, and diabetes. During feeding, gut microbes produce short-chain fatty acids, which are important energy sources for the host. Here we show that the short-chain fatty acid receptor GPR43 links the metabolic activity of the gut microbiota with host body energy homoeostasis. We demonstrate that GPR43-deficient mice are obese on a normal diet, whereas mice overexpressing GPR43 specifically in adipose tissue remain lean even when fed a high-fat diet. Raised under germ-free conditions or after treatment with antibiotics, both types of mice have a normal phenotype. We further show that short-chain fatty acid-mediated activation of GPR43 suppresses insulin signalling in adipocytes, which inhibits fat accumulation in adipose tissue and promotes the metabolism of unincorporated lipids and glucose in other tissues. These findings establish GPR43 as a sensor for excessive dietary energy, thereby controlling body energy utilization while maintaining metabolic homoeostasis.

1,052 citations



Journal ArticleDOI
09 Aug 2013-Science
TL;DR: This work reviews the progress that has been made in making sequence-controlled polymers of increasing length and complexity and proposes some strategies for controlling sequences in chain-growth and step-growth polymerizations.
Abstract: Background During the last few decades, progress has been made in manipulating the architecture of synthetic polymer materials. However, the primary structure—that is, the sequential arrangement of monomer units in a polymer chain—is generally poorly controlled in synthetic macromolecules. Common synthetic polymers are usually homopolymers, made of the same monomer unit, or copolymers with simple chain microstructures, such as random or block copolymers. These polymers are used in many areas but do not have the structural and functional complexity of sequence-defined biopolymers, such as nucleic acids or proteins. Indeed, monomer sequence regulation plays a key role in biology and is a prerequisite for crucial features of life, such as heredity, self-replication, complex self-assembly, and molecular recognition. In this context, developing synthetic polymers containing controlled monomer sequences is an important area for research. Precise molecular encoding of synthetic polymer chains. In most synthetic copolymers, monomer units (represented here as colored square boxes A, B, C, and D) are distributed randomly along the polymer chains (left). In sequence-controlled polymers, they are arranged in a specific order in all of the chains (right). Monomer sequence regularity strongly influences the molecular, supramolecular, andmacroscopic properties of polymer materials. Advances Various synthetic methods for controlling monomer sequences in polymers have been identified, and two major trends in the field of sequence-controlled polymers have emerged. Some approaches use biological concepts that have been optimized by nature for sequence regulation. For instance, DNA templates, enzymes, or even living organisms can be used to prepare sequence-defined polymers. These natural mechanisms can be adapted to tolerate nonnatural monomers. The other trend is the preparation of sequence-controlled polymers by synthetic chemistry. In the most popular approach, monomer units are attached one by one to a support, which is an efficient method but demanding in practice. Recently, some strategies have been proposed for controlling sequences in chain-growth and step-growth polymerizations. These mechanisms usually allow fast and large-scale synthesis of polymers. Specific kinetics and particular catalytic or template conditions allow sequence regulation in these processes. Outlook The possibility of controlling monomer sequences in synthetic macromolecules has many scientific and technological implications. Information can be controlled at the molecular level in synthetic polymer chains. This opens up interesting perspectives for the field of data storage. In addition, having power over monomer sequences could mean structural control of the resulting polymer, as it strongly influences macromolecular folding and self-assembly. For instance, functional synthetic assemblies that mimic the properties of globular proteins, such as enzymes and transporters, can be foreseen. Moreover, monomer sequence control influences some macroscopic properties. For example, bulk properties such as conductivity, rigidity, elasticity, or biodegradability can be finely tuned in sequence-controlled polymers. The behavior of polymers in solution, particularly in water, is also strongly dependent on monomer sequences. Thus, sequence regulation may enable a more effective control of structure-property relations in tomorrow’s polymer materials.

1,008 citations


Journal ArticleDOI
TL;DR: This integrated molecular analysis of clear-cell renal cell carcinoma unmasked new correlations between DNA methylation, gene mutation and/or gene expression and copy number profiles, enabling the stratification of clinical risks for patients with ccRCC.
Abstract: Clear-cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer and its molecular pathogenesis is incompletely understood. Here we report an integrated molecular study of ccRCC in which ≥100 ccRCC cases were fully analyzed by whole-genome and/or whole-exome and RNA sequencing as well as by array-based gene expression, copy number and/or methylation analyses. We identified a full spectrum of genetic lesions and analyzed gene expression and DNA methylation signatures and determined their impact on tumor behavior. Defective VHL-mediated proteolysis was a common feature of ccRCC, which was caused not only by VHL inactivation but also by new hotspot TCEB1 mutations, which abolished Elongin C-VHL binding, leading to HIF accumulation. Other newly identified pathways and components recurrently mutated in ccRCC included PI3K-AKT-mTOR signaling, the KEAP1-NRF2-CUL3 apparatus, DNA methylation, p53-related pathways and mRNA processing. This integrated molecular analysis unmasked new correlations between DNA methylation, gene mutation and/or gene expression and copy number profiles, enabling the stratification of clinical risks for patients with ccRCC.

Journal ArticleDOI
A. A. Abdo1, A. A. Abdo2, Marco Ajello3, Alice Allafort4  +254 moreInstitutions (60)
TL;DR: In this article, a catalog of gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite is presented.
Abstract: This catalog summarizes 117 high-confidence > 0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data, through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.

Journal ArticleDOI
17 Jan 2013-Cell
TL;DR: This work demonstrates that NF-κB modulates Wnt signaling and shows that IEC-specific ablation of RelA/p65 retards crypt stem cell expansion and highlights the importance of inflammatory signaling for dedifferentiation and generation of tumor-initiating cells in vivo.

Journal ArticleDOI
TL;DR: A set of terms, definitions, and recommendations for use in the classi- fication of coordination polymers, networks, and metal-organic frameworks (MOFs) is provided in this paper.
Abstract: A set of terms, definitions, and recommendations is provided for use in the classi- fication of coordination polymers, networks, and metal-organic frameworks (MOFs). A hier- archical terminology is recommended in which the most general term is coordination poly- mer. Coordination networks are a subset of coordination polymers and MOFs a further subset of coordination networks. One of the criteria an MOF needs to fulfill is that it contains poten- tial voids, but no physical measurements of porosity or other properties are demanded per se. The use of topology and topology descriptors to enhance the description of crystal structures of MOFs and 3D-coordination polymers is furthermore strongly recommended.

Journal ArticleDOI
TL;DR: In this article, the electric and magnetic fields of intense terahertz transients can be used to control matter and light, and the fundamental interaction mechanisms of terrahertz radiation with matter are discussed.
Abstract: This article provides an overview and illustrative examples of how the electric and magnetic fields of intense terahertz transients can be used to resonantly, and even nonresonantly, control matter and light. It discusses the fundamental interaction mechanisms of intense terahertz radiation with matter.

Journal ArticleDOI
Markus Ackermann, Marco Ajello1, Alice Allafort2, Luca Baldini3  +197 moreInstitutions (42)
15 Feb 2013-Science
TL;DR: The characteristic pion-decay feature is detected in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope, providing direct evidence that cosmic-ray protons are accelerated in SNRs.
Abstract: Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.

Journal ArticleDOI
TL;DR: It is concluded that a substantial improvement in the quality of model predictions can be achieved if uneven sampling effort is taken into account, thereby improving the efficacy of species conservation planning.
Abstract: Aim Advancement in ecological methods predicting species distributions is a crucial precondition for deriving sound management actions. Maximum entropy (MaxEnt) models are a popular tool to predict species distributions, as they are considered able to cope well with sparse, irregularly sampled data and minor location errors. Although a fundamental assumption of MaxEnt is that the entire area of interest has been systematically sampled, in practice, MaxEnt models are usually built from occurrence records that are spatially biased towards better-surveyed areas. Two common, yet not compared, strategies to cope with uneven sampling effort are spatial filtering of occurrence data and background manipulation using environmental data with the same spatial bias as occurrence data. We tested these strategies using simulated data and a recently collated dataset on Malay civet Viverra tangalunga in Borneo. Location Borneo, Southeast Asia. Methods We collated 504 occurrence records of Malay civets from Borneo of which 291 records were from 2001 to 2011 and used them in the MaxEnt analysis (baseline scenario) together with 25 environmental input variables. We simulated datasets for two virtual species (similar to a range-restricted highland and a lowland species) using the same number of records for model building. As occurrence records were biased towards north-eastern Borneo, we investigated the efficacy of spatial filtering versus background manipulation to reduce overprediction or underprediction in specific areas. Results Spatial filtering minimized omission errors (false negatives) and commission errors (false positives). We recommend that when sample size is insufficient to allow spatial filtering, manipulation of the background dataset is preferable to not correcting for sampling bias, although predictions were comparatively weak and commission errors increased. Main Conclusions We conclude that a substantial improvement in the quality of model predictions can be achieved if uneven sampling effort is taken into account, thereby improving the efficacy of species conservation planning.

Journal ArticleDOI
TL;DR: A water-based optical clearing agent, SeeDB, is reported, which clears fixed brain samples in a few days without quenching many types of fluorescent dyes, including fluorescent proteins and lipophilic neuronal tracers.
Abstract: This technical report describes a method to clear fixed brain tissues while allowing for fluorescent dye tracing and retaining cellular morphology. The authors demonstrate the utility of the technique by obtaining a wiring diagram for sister mitral cells.

Journal ArticleDOI
TL;DR: The molecular mechanisms of the functions of PD-1, in conjunction with the mild, chronic and strain-specific autoimmune phenotypes ofPD-1-deficient mice, suggest that immunoregulation by PD- 1 is rather antigen specific and is mainly cell intrinsic.
Abstract: PD-1, a negative coreceptor expressed on antigen-stimulated T cells and B cells, seems to serve as a 'rheostat' of the immune response. The molecular mechanisms of the functions of PD-1, in conjunction with the mild, chronic and strain-specific autoimmune phenotypes of PD-1-deficient mice, in contrast to the devastating fatal autoimmune disease of mice deficient in the immunomodulatory receptor CTLA-4, suggest that immunoregulation by PD-1 is rather antigen specific and is mainly cell intrinsic. Such unique properties make PD-1 a powerful target for immunological therapy, with highly effective clinical applications for cancer treatment.

Journal ArticleDOI
07 Nov 2013-Cell
TL;DR: It is reported that inhibition of transmethylation reactions elongates the circadian period and methylation inhibition causes widespread changes in the transcription of the RNA processing machinery, associated with m(6)A-RNA methylation.

Journal ArticleDOI
Joao Almeida1, Joao Almeida2, Siegfried Schobesberger3, Andreas Kürten1, Ismael K. Ortega3, Oona Kupiainen-Määttä3, Arnaud P. Praplan4, Alexey Adamov3, António Amorim5, F. Bianchi4, Martin Breitenlechner6, A. David2, Josef Dommen4, Neil M. Donahue7, Andrew J. Downard8, Eimear M. Dunne9, Jonathan Duplissy3, Sebastian Ehrhart1, Richard C. Flagan8, Alessandro Franchin3, Roberto Guida2, Jani Hakala3, Armin Hansel6, Martin Heinritzi6, Henning Henschel3, Tuija Jokinen3, Heikki Junninen3, Maija Kajos3, Juha Kangasluoma3, Helmi Keskinen10, Agnieszka Kupc11, Theo Kurtén3, Alexander N. Kvashin12, Ari Laaksonen10, Ari Laaksonen13, Katrianne Lehtipalo3, Markus Leiminger1, Johannes Leppä13, Ville Loukonen3, Vladimir Makhmutov12, Serge Mathot2, Matthew J. McGrath14, Tuomo Nieminen3, Tuomo Nieminen15, Tinja Olenius3, Antti Onnela2, Tuukka Petäjä3, Francesco Riccobono4, Ilona Riipinen16, Matti P. Rissanen3, Linda Rondo1, Taina Ruuskanen3, Filipe Duarte Santos5, Nina Sarnela3, Simon Schallhart3, R. Schnitzhofer6, John H. Seinfeld8, Mario Simon1, Mikko Sipilä15, Mikko Sipilä3, Yuri Stozhkov12, Frank Stratmann17, António Tomé5, Jasmin Tröstl4, Georgios Tsagkogeorgas17, Petri Vaattovaara10, Yrjö Viisanen13, Annele Virtanen10, Aron Vrtala11, Paul E. Wagner11, Ernest Weingartner4, Heike Wex17, Christina Williamson1, Daniela Wimmer1, Daniela Wimmer3, Penglin Ye7, Taina Yli-Juuti3, Kenneth S. Carslaw9, Markku Kulmala3, Markku Kulmala15, Joachim Curtius1, Urs Baltensperger4, Douglas R. Worsnop, Hanna Vehkamäki3, Jasper Kirkby1, Jasper Kirkby2 
17 Oct 2013-Nature
TL;DR: The results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
Abstract: Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sun ...

Journal ArticleDOI
TL;DR: New self-organizing aspects of human corticogenesis are shown: spontaneous development of intracortical polarity, curving morphology, and complex zone separations, which suggest human neocorticogenesis involves intrinsic programs that enable the emergence of complex neocortical features.
Abstract: Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaudal-ventrorostral axis and undergoes region-specific rolling morphogenesis that generates a semispherical structure. The neuroepithelium self-forms a multilayered structure including three neuronal zones (subplate, cortical plate, and Cajal-Retzius cell zones) and three progenitor zones (ventricular, subventricular, and intermediate zones) in the same apical-basal order as seen in the human fetal cortex in the early second trimester. In the cortical plate, late-born neurons tend to localize more basally to early-born neurons, consistent with the inside-out pattern seen in vivo. Furthermore, the outer subventricular zone contains basal progenitors that share characteristics with outer radial glia abundantly found in the human, but not mouse, fetal brain. Thus, human neocorticogenesis involves intrinsic programs that enable the emergence of complex neocortical features.

Journal ArticleDOI
B. S. Acharya1, Marcos Daniel Actis2, T. Aghajani3, G. Agnetta4  +979 moreInstitutions (122)
TL;DR: The Cherenkov Telescope Array (CTA) as discussed by the authors is a very high-energy (VHE) gamma ray observatory with an international collaboration with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America.

Journal ArticleDOI
TL;DR: The state-of-the-art of studies of ion conductivity by PCP/MOFs and nonporous coordination polymers (CPs) are described and future perspectives are offered.
Abstract: Ion conduction and transport in solids are both interesting and useful and are found in widely distinct materials, from those in battery-related technologies to those in biological systems. Scientists have approached the synthesis of ion-conductive compounds in a variety of ways, in the areas of organic and inorganic chemistry. Recently, based on their ion-conducting behavior, porous coordination polymers (PCPs) and metal–organic frameworks (MOFs) have been recognized for their easy design and the dynamic behavior of the ionic components in the structures. These PCP/MOFs consist of metal ions (or clusters) and organic ligands structured via coordination bonds. They could have highly concentrated mobile ions with dynamic behavior, and their characteristics have inspired the design of a new class of ion conductors and transporters.In this Account, we describe the state-of-the-art of studies of ion conductivity by PCP/MOFs and nonporous coordination polymers (CPs) and offer future perspectives. PCP/MOF struc...

Journal ArticleDOI
TL;DR: It is suggested that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone the authors consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance.
Abstract: Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance.

Journal ArticleDOI
TL;DR: Differential manifestation of ER stress and DHA responsiveness may help explain variable clinical results obtained with the use of DHA treatment and suggests that DHA may in fact be effective for a subset of patients.

Journal ArticleDOI
21 Mar 2013-Immunity
TL;DR: Understanding how epigenetic alterations and Foxp3 expression coordinately control Treg-cell-specific gene regulation will enable better control of immune responses by targeting the generation and maintenance of Treg cells.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah  +2942 moreInstitutions (201)
TL;DR: In this paper, the spin and parity quantum numbers of the Higgs boson were studied based on the collision data collected by the ATLAS experiment at the LHC, and the results showed that the standard model spin-parity J(...

Journal ArticleDOI
TL;DR: A modified protocol enabling efficient iPSC induction from CD34+ cord blood cells and from peripheral blood isolated from healthy donors using these plasmid vectors is reported, which enabled the establishment of blood‐derived iPSCs from seven healthy donors ranging in age from their 20s to their 60s.
Abstract: The generation of induced pluripotent stem cells (iPSCs) provides the opportunity to use patient-specific somatic cells, which are a valuable source for disease modeling and drug discovery. To promote research involving these cells, it is important to make iPSCs from easily accessible and less invasive tissues, like blood. We have recently reported the efficient generation of human iPSCs from adult fibroblasts using a combination of plasmids encoding OCT3/4, SOX2, KLF4, L-MYC, LIN28, and shRNA for TP53. We herein report a modified protocol enabling efficient iPSC induction from CD34+ cord blood cells and from peripheral blood isolated from healthy donors using these plasmid vectors. The original plasmid mixture could induce iPSCs; however, the efficiency was low. The addition of EBNA1, an essential factor for episomal amplification of the vectors, by an extra plasmid greatly increased the efficiency of iPSC induction, especially when the induction was performed from αβT cells. This improvement enabled the establishment of blood-derived iPSCs from seven healthy donors ranging in age from their 20s to their 60s. This induction method will be useful for the derivation of patient-specific integration-free iPSCs and would also be applicable to the generation of clinical-grade iPSCs in the future.

Journal ArticleDOI
TL;DR: In this paper, an organic host-guest material with efficient persistent RT phosphorescence (RTP) was developed by minimizing the nonradiative deactivation pathway of triplet excitons.
Abstract: Persistent emission with a long lifetime (>1 s) from organic materials can only be observed at a low temperature, because of the significant nonradiative deactivation pathway that occurs at room-temperature (RT). If organic materials with persistent RT emission in air could be developed, they could potentially be utilized for a variety of applications. Here, organic host-guest materials with efficient persistent RT phosphorescence (RTP) are developed by minimizing the nonradiative deactivation pathway of triplet excitons. The nonradiative deactivation pathway is dependent on both nonradiative deactivation of the guest and quenching by diffusional motion of the host. The rigidity and oxygen barrier properties of the steroidal compound used as the host suppressed the quenching, and the aromatic hydrocarbon used as the guest is highly deuterated to minimize nonradiative deactivation of the guest. Red-green-blue persistent RTP with a lifetime >1 s and a quantum yield >10% in air is realized for a pure organic material.