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Showing papers by "Collège de France published in 2016"


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +961 moreInstitutions (100)
TL;DR: The discovery of the GW150914 with the Advanced LIGO detectors provides the first observational evidence for the existence of binary black-hole systems that inspiral and merge within the age of the Universe as mentioned in this paper.
Abstract: The discovery of the gravitational-wave source GW150914 with the Advanced LIGO detectors provides the first observational evidence for the existence of binary black-hole systems that inspiral and merge within the age of the Universe. Such black-hole mergers have been predicted in two main types of formation models, involving isolated binaries in galactic fields or dynamical interactions in young and old dense stellar environments. The measured masses robustly demonstrate that relatively "heavy" black holes (≳25M⊙) can form in nature. This discovery implies relatively weak massive-star winds and thus the formation of GW150914 in an environment with metallicity lower than ∼1/2 of the solar value. The rate of binary black-hole mergers inferred from the observation of GW150914 is consistent with the higher end of rate predictions (≳1Gpc−3yr−1) from both types of formation models. The low measured redshift (z∼0.1) of GW150914 and the low inferred metallicity of the stellar progenitor imply either binary black-hole formation in a low-mass galaxy in the local Universe and a prompt merger, or formation at high redshift with a time delay between formation and merger of several Gyr. This discovery motivates further studies of binary-black-hole formation astrophysics. It also has implications for future detections and studies by Advanced LIGO and Advanced Virgo, and gravitational-wave detectors in space.

742 citations


Journal ArticleDOI
TL;DR: In this article, the authors summarized various design strategies for producing random, aligned and core/shell structured carbon nanofibers, and elucidated the influences of polymer precursors, processing parameters, conductive additives and catalysts on functional, morphological and structural characteristics of CNFs.

548 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +955 moreInstitutions (96)
TL;DR: Following a major upgrade, the two advanced detectors of the Laser Interferometer Gravitational-wave Observatory (LIGO) held their first observation run between September 2015 and January 2016, and observed a transient gravitational-wave signal determined to be the coalescence of two black holes.
Abstract: Following a major upgrade, the two advanced detectors of the Laser Interferometer Gravitational-wave Observatory (LIGO) held their first observation run between September 2015 and January 2016. With a strain sensitivity of $10^{-23}/\sqrt{\mathrm{Hz}}$ at 100 Hz, the product of observable volume and measurement time exceeded that of all previous runs within the first 16 days of coincident observation. On September 14th, 2015 the Advanced LIGO detectors observed a transient gravitational-wave signal determined to be the coalescence of two black holes [Phys. Rev. Lett. 116, 061102 (2016)], launching the era of gravitational-wave astronomy. The event, GW150914, was observed with a combined signal-to-noise ratio of 24 in coincidence by the two detectors. Here we present the main features of the detectors that enabled this observation. At full sensitivity, the Advanced LIGO detectors are designed to deliver another factor of three improvement in the signal-to-noise ratio for binary black hole systems similar in masses to GW150914.

539 citations


Journal ArticleDOI
TL;DR: Understanding and controlling anionic redox processes is pivotal for the design of new Li-ion battery and water-splitting materials and will help improve the quality of existing and new lithium-ion batteries.
Abstract: Understanding and controlling the anionic redox processes is pivotal for the design of new Li-ion battery and water splitting materials.

502 citations


Journal ArticleDOI
TL;DR: In this paper, the ability of Li-ion batteries to stabilize the oxygen holes generated by Li-removal and to achieve a reversible oxo-to peroxo-like (2O2−/(O2)n−) transformation is elucidated by means of a metal-driven reductive coupling mechanism.
Abstract: The energy density delivered by a Li-ion battery is a key parameter that needs to be significantly increased to address the global question of energy storage for the next 40 years. This quantity is directly proportional to the battery voltage (V) and the battery capacity (C) which are difficult to improve simultaneously when materials exhibit classical cationic redox activity. Recently, a cumulative cationic (M4+/M5+) and anionic (2O2−/(O2)n−) redox activity has been demonstrated in the Li-rich Li2MO3 family of compounds, therefore enabling doubling of the energy density with respect to high-potential cathodes such as transition metal phosphates and sulfates. This paper aims to clarify the origin of this extra capacity by addressing some fundamental questions regarding reversible anionic redox in high-potential electrodes for Li-ion batteries. First, the ability of the system to stabilize the oxygen holes generated by Li-removal and to achieve a reversible oxo- to peroxo-like (2O2−/(O2)n−) transformation is elucidated by means of a metal-driven reductive coupling mechanism. The penchant of the system for undergoing this reversible anionic redox or releasing O2 gas is then discussed with regards to experimental results for 3d- and 4d-based Li2MO3 phases. Finally, robust indicators are built as tools to predict which materials in the Li-rich TM-oxide family will undergo efficient and reversible anionic redox. The present finding provides insights into new directions to be explored for the development of high-energy density materials for Li-ion batteries.

417 citations


Journal ArticleDOI
18 Jul 2016-Nature
TL;DR: A crucial role is demonstrated for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC–seq) and RNA sequencing, and deletion of the boundary disrupts mega-domain formation.
Abstract: X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD-like structures after XCI. These findings suggest a key role for transcription and CTCF in the formation of TADs in the context of the Xi chromosome in neural progenitors.

355 citations


Journal ArticleDOI
TL;DR: In this article, a single voltage Na uptake plateau at similar or equal to 0.1 V with a capacity of 200 mAh g(-1) for CNFs carbonized at above 2000 degrees C. This specific performance may be nested in the higher degree of graphitization, lower active surface area, and different porous texture of the carbon nanofibers.
Abstract: Hard carbons are considered among the most promising anode materials for Na-ion batteries. Understanding their structure is of great importance for optimizing their Na storage capabilities and therefore achieving high performance. Herein, carbon nanofibers (CNFs) are prepared by electrospinning and their microstructure, texture, and surface functionality are tailored through carbonization at various temperatures ranging from 650 to 2800 degrees C. Stepwise carbonization gradually removes the heteroatoms and increases the graphitization degree, enabling us to monitor the corresponding electrochemical performance for establishing a correlation between the CNFs characteristics and Na storage behavior. Outstandingly, it is found that for CNFs carbonized at above 2000 degrees C, a single voltage Na uptake plateau at similar or equal to 0.1 V with a capacity of similar or equal to 200 mAh g(-1). This specific performance may be nested in the higher degree of graphitization, lower active surface area, and different porous texture of the CNFs at such temperatures. It is demonstrated via the assembly of a CNF/Na2Fe2(SO4)(3) cell the benefit of such CNFs electrode for enhancing the energy density of full Na-ion cells. This finding sheds new insights in the quest for high performance carbon based anode materials.

342 citations


Journal ArticleDOI
TL;DR: The authors show that standard theories, which build on a random growth mechanism, generate transition dynamics that are too slow relative to those observed in the data and suggest two parsimonious deviations from the canonical model that can explain such changes: scale dependence that may arise from changes in skill prices and type dependence, that is, the presence of some high-growth types.
Abstract: The past forty years have seen a rapid rise in top income inequality in the United States While there is a large number of existing theories of the Pareto tail of the long-run income distributions, almost none of these address the fast rise in top inequality observed in the data We show that standard theories, which build on a random growth mechanism, generate transition dynamics that are too slow relative to those observed in the data We then suggest two parsimonious deviations from the canonical model that can explain such changes: “scale dependence” that may arise from changes in skill prices, and “type dependence,” that is, the presence of some “high-growth types” These deviations are consistent with theories in which the increase in top income inequality is driven by the rise of “superstar” entrepreneurs or managers

297 citations


Journal ArticleDOI
25 Aug 2016-Cell
TL;DR: Four major receptor families enable cells to respond to chemical and physical signals from their proximal environment, and recent studies point to common mechanisms governing the allosteric transitions of these receptors, including the impact of oligomerization, pre-existing and functionally distinct conformational ensembles, intrinsically disordered regions, and the occurrence ofallosteric modulatory sites.

223 citations


Journal ArticleDOI
TL;DR: This code is mainly designed to be used with the TRIQS library in order to solve the self-consistent quantum impurity problem in a multi-orbital dynamical mean field theory approach to strongly-correlated electrons, in particular in the context of realistic electronic structure calculations.

207 citations


Journal ArticleDOI
TL;DR: An easily scalable ball milling approach, which relies on the use of metallic sodium, to prepare a variety of sodium-based alloys, insertion layered oxides and polyanionic compounds having sodium in excess such as the Na4V2(PO4)2F3 phase, which may offer electrode design principles for accelerating the development of the sodium-ion technology.
Abstract: Sodium-ion batteries have been considered as potential candidates for stationary energy storage because of the low cost and wide availability of Na sources. However, their future commercialization depends critically on control over the solid electrolyte interface formation, as well as the degree of sodiation at the positive electrode. Here we report an easily scalable ball milling approach, which relies on the use of metallic sodium, to prepare a variety of sodium-based alloys, insertion layered oxides and polyanionic compounds having sodium in excess such as the Na4V2(PO4)2F3 phase. The practical benefits of preparing sodium-enriched positive electrodes as reservoirs to compensate for sodium loss during solid electrolyte interphase formation are demonstrated by assembling full C/P'2-Na1[Fe0.5Mn0.5]O2 and C/'Na3+xV2(PO4)2F3' sodium-ion cells that show substantial increases (>10%) in energy storage density. Our findings may offer electrode design principles for accelerating the development of the sodium-ion technology.

Journal ArticleDOI
TL;DR: The field of hybrid inorganic-organic materials has experienced an explosive growth since the 1980s, with the expansion of soft inorganic chemistry based processes as discussed by the authors, and a high degree of control over both composition and nanostructure of these hybrids can be achieved allowing tunable structure-property relationships.
Abstract: Research on hybrid inorganic-organic materials has experienced an explosive growth since the 1980s, with the expansion of soft inorganic chemistry based processes. Indeed, mild synthetic conditions, low processing temperatures provided by “chimie douce” and the versatility of the colloidal state allow for the mixing of the organic and inorganic components at the nanometer scale in virtually any ratio to produce the so called hybrid materials. Today a high degree of control over both composition and nanostructure of these hybrids can be achieved allowing tunable structure-property relationships. This, in turn, makes it possible to tailor and fine-tune many properties (mechanical, optical, electronic, thermal, chemical…) in very broad ranges, and to design specific multifunctional systems for applications. In particular, the field of “Hybrid-Optics” has been very productive not only scientifically but also in terms of applications. Indeed, numerous optical devices based on hybrids are already in, or very close, to the market. This review describes most of the recent advances performed in this field. Emphasis will be given to luminescent, photochromic, NLO and plasmonic properties. As an outlook we show that the controlled coupling between plasmonics and luminescence is opening a land of opportunities in the field of “Hybrid-Optics”.

Journal ArticleDOI
TL;DR: Microsized Sn presents stable cyclic performance in a glyme-based electrolyte, which brings 19% increase in energy density of Sn/Na3 V2 (PO4 )3 cells as compared to the cells using a hard carbon anode.
Abstract: Microsized Sn presents stable cyclic performance in a glyme-based electrolyte, which brings 19% increase in energy density of Sn/Na3 V2 (PO4 )3 cells as compared to the cells using a hard carbon anode. The NaSn intermediate phases are also clarified.

Journal ArticleDOI
TL;DR: It is shown that a short period of consumption of high-fat diet alters the small-intestinal defenses and that the biochemistry of the ileum is drastically modified, leading to physiological changes close to that observed in cystic fibrosis.
Abstract: Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum—which is usually described as free of bacteria—became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus. A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ–deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.

Journal ArticleDOI
07 Dec 2016-Neuron
TL;DR: The neural dynamics underlying the maintenance of variably visible stimuli using magnetoencephalography are investigated and it is suggested that invisible information can be briefly maintained within the higher processing stages of visual perception.

Journal ArticleDOI
TL;DR: The authors acknowledge EC for funding through H2020 NAIADES project (LCE10-2014, Contract number 646433), L. Simonin and Y. Chatillon from CEA for sending the Na3V2(PO4)2F3 materials, and members of both the RS2E Na-ion task force and ALISTORE-ERI======
Abstract: Authors acknowledge EC for funding through H2020 NAIADES project (LCE10-2014, Contract number 646433), L. Simonin and Y. Chatillon from CEA for sending the Na3V2(PO4)2F3 materials, and members of both the RS2E Na-ion task force and ALISTORE-ERI for fruitful discussions.

Journal ArticleDOI
TL;DR: In this paper, the dynamics of a phonon-mediated superconductor driven out of equilibrium were investigated by solving the Migdal-Eliashberg equations for the double-time Keldysh Green's functions.
Abstract: We investigate the dynamics of a phonon-mediated superconductor driven out of equilibrium. The electronic hopping amplitude is ramped down in time, resulting in an increased electronic density of states. The dynamics of the coupled electron-phonon model is investigated by solving Migdal-Eliashberg equations for the double-time Keldysh Green's functions. The increase of the density of states near the Fermi level leads to an enhancement of superconductivity when the system thermalizes to the new state at the same temperature. We provide a time- and momentum-resolved view on this thermalization process and show that it involves fast processes associated with single-particle scattering and much slower dynamics associated with the superconducting order parameter. The importance of electron-phonon coupling for the rapid enhancement and the efficient thermalization of superconductivity is demonstrated, and the results are compared to a BCS time-dependent mean-field approximation.

Journal ArticleDOI
TL;DR: An application based on the TRIQS library that connects this toolbox to realistic materials calculations based on density functional theory (DFT) and supplies tools and methods to construct Wannier functions and to perform the DMFT self-consistency cycle in this basis set.

Journal ArticleDOI
Abstract: Li-rich layered oxides, e.g. Li[Li 0.20 Ni 0.13 Mn 0.54 Co 0.13 ]O 2 (LR-NMC), lead high energy density Li-ion battery cathodes, thanks to the reversible redox of oxygen anions that boost charge storage capacity. Unfortunately, their commercialization has been stalled by practical issues (i.e. voltage hysteresis, poor rate capability, and voltage fade) and hence it is necessary to investigate whether these problems are intrinsically inherent to anionic redox and its structural consequences. To this end, the 'model' Li-rich layered oxide Li 2 Ru 0.75 Sn 0.25 O 3 (LRSO) is here used as a fertile test-bed for scrutinizing the effects of cationic and anionic redox independently since they are neatly isolated at low and high potentials, respectively. Through an arsenal of electrochemical techniques, we demonstrate that voltage hysteresis is triggered by anionic redox and grows progressively with deeper oxidation of oxygen in conjunction with the deterioration of both interfacial charge-transfer kinetics and bulk diffusion coefficient. We equally show that this anionic-driven poor kinetics keeps deteriorating further with cycling and we also find that voltage fades faster if oxygen is kept oxidized for longer. Our findings, which are in fact harsher for LR-NMC, convey caution that anionic redox risks practical problems; hence, when chasing larger capacities with this class of materials, we encourage considering real-world applications.

Journal ArticleDOI
TL;DR: It is concluded that ACE2 represents a major negative regulator of apelin action in the vasculature and heart and designed and synthesized active apelin analogues that were resistant to ACE2-mediated degradation, thereby confirming that stable apelin analogueues can be designed as potential drugs.
Abstract: Apelin peptides mediate beneficial effects on the cardiovascular system and are being targeted as potential new drugs. However, apelin peptides have extremely short biological half-lives, and improved understanding of apelin peptide metabolism may lead to the discovery of biologically stable analogues with therapeutic potential. We examined the ability of angiotensin-converting enzyme 2 (ACE2) to cleave and inactivate pyr-apelin 13 and apelin 17, the dominant apelin peptides. Computer-assisted modeling shows a conserved binding of pyr-apelin 13 and apelin 17 to the ACE2 catalytic site. In ACE2 knockout mice, hypotensive action of pyr-apelin 13 and apelin 17 was potentiated, with a corresponding greater elevation in plasma apelin levels. Similarly, pharmacological inhibition of ACE2 potentiated the vasodepressor action of apelin peptides. Biochemical analysis confirmed that recombinant human ACE2 can cleave pyr-apelin 13 and apelin 17 efficiently, and apelin peptides are degraded slower in ACE2-deficient plasma. The biological relevance of ACE2-mediated proteolytic processing of apelin peptides was further supported by the reduced potency of pyr-apelin 12 and apelin 16 on the activation of signaling pathways and nitric oxide production from endothelial cells. Importantly, although pyr-apelin 13 and apelin 17 rescued contractile function in a myocardial ischemia-reperfusion model, ACE2 cleavage products, pyr-apelin 12 and 16, were devoid of these cardioprotective effects. We designed and synthesized active apelin analogues that were resistant to ACE2-mediated degradation, thereby confirming that stable apelin analogues can be designed as potential drugs. We conclude that ACE2 represents a major negative regulator of apelin action in the vasculature and heart.

Journal ArticleDOI
TL;DR: In this paper, the authors reported the electrochemical properties of a Na-rich phase Na2IrO3 which can reversibly cycle 1.5 Na+ per formula unit while not suffering from oxygen release nor cationic migrations.
Abstract: The recent revival of the Na-ion battery concept has prompted intense activities in the search for new Na-based layered oxide positive electrodes. The largest capacity to date was obtained for a Na-deficient layered oxide that relies on cationic redox processes only. To go beyond this limit, we decided to chemically manipulate these Na-based layered compounds in a way to trigger the participation of the anionic network. We herein report the electrochemical properties of a Na-rich phase Na2IrO3, which can reversibly cycle 1.5 Na+ per formula unit while not suffering from oxygen release nor cationic migrations. Such large capacities, as deduced by complementary XPS, X-ray/neutron diffraction and transmission electron microscopy measurements, arise from cumulative cationic and anionic redox processes occurring simultaneously at potentials as low as 2.7 V vs Na+/Na. The inability to remove more than 1.5 Na+ is rooted in the formation of an O1-type phase having highly stabilized Na sites as confirmed by DFT calculations, which could rationalize as well the competing metal/oxygen redox processes in Na2IrO3. This work will help to define the most fertile directions in the search for novel high energy Na-rich materials based on more sustainable elements than Ir.

Journal ArticleDOI
TL;DR: Several independent prognostic factors are identified that can guide the management of R/R PCNSL patients after first-line therapy in a nationwide cohort of patients.
Abstract: BACKGROUND: Treatment of relapsed/refractory (R/R) primary CNS lymphoma (PCNSL) is poorly defined, because randomized trials and large studies are lacking. The aim of this study was to analyze the characteristics, management, and outcome of R/R PCNSL patients after first-line therapy in a nationwide cohort. METHODS: We analyzed R/R PCNSL patients following first-line treatment who had been prospectively registered in the database of the French network for oculocerebral lymphoma (LOC) between 2011 and 2014. RESULTS: Among 563 PCNSL patients treated with first-line therapy, we identified 256 with relapsed (n = 93, 16.5%) or refractory (n = 163, 29.0%) disease. Patients who were asymptomatic at relapse/progression (25.5%), mostly diagnosed on routine follow-up neuroimaging, tended to have a better outcome. Patients who received salvage therapy followed by consolidation (mostly intensive chemotherapy plus autologous hematopoietic stem cell transplantation [ICT + AHSCT]) experienced prolonged survival compared with those who did not receive salvage or consolidation therapy. Independent prognostic factors at first relapse/progression were: KPS ≥ 70 vs KPS \textless 70), sensitivity to first-line therapy (relapsed vs refractory disease), duration of first remission (progression-free survival [PFS] ≥1 y vs \textless1 y), and management at relapse/progression (palliative care vs salvage therapy). Patients who relapsed early after first-line therapy (ie, PFS \textless 1 y) had a poor outcome, comparable to that of refractory patients. Conversely, patients experiencing late relapses (PFS ≥ 1 y) and/or undergoing consolidation with ICT + AHSCT experienced prolonged survival. CONCLUSIONS: About a third of PCNSL patients are primary refractory to first line treatment. We identified several independent prognostic factors that can guide the management of R/R PCNSL patients

Journal ArticleDOI
29 Jan 2016-Brain
TL;DR: Restoration of CYP46A1 re-establishes normal cholesterol levels and is neuroprotective, suggesting that targeting cholesterol degradation may have therapeutic potential.
Abstract: Huntington’s disease is an autosomal dominant neurodegenerative disease caused by abnormal polyglutamine expansion in huntingtin (Exp-HTT) leading to degeneration of striatal neurons. Altered brain cholesterol homeostasis has been implicated in Huntington’s disease, with increased accumulation of cholesterol in striatal neurons yet reduced levels of cholesterol metabolic precursors. To elucidate these two seemingly opposing dysregulations, we investigated the expression of cholesterol 24-hydroxylase (CYP46A1), the neuronal-specific and rate-limiting enzyme for cholesterol conversion to 24S-hydroxycholesterol (24S-OHC). CYP46A1 protein levels were decreased in the putamen, but not cerebral cortex samples, of post-mortem Huntington’s disease patients when compared to controls. Cyp46A1 mRNA and CYP46A1 protein levels were also decreased in the striatum of the R6/2 Huntington’s disease mouse model and in SThdhQ111 cell lines. In vivo, in a wild-type context, knocking down CYP46A1 expression in the striatum, via an adeno-associated virus-mediated delivery of selective shCYP46A1, reproduced the Huntington’s disease phenotype, with spontaneous striatal neuron degeneration and motor deficits, as assessed by rotarod. In vitro, CYP46A1 restoration protected SThdhQ111 and Exp-HTT-expressing striatal neurons in culture from cell death. In the R6/2 Huntington’s disease mouse model, adeno-associated virus-mediated delivery of CYP46A1 into the striatum decreased neuronal atrophy, decreased the number, intensity level and size of Exp-HTT aggregates and improved motor deficits, as assessed by rotarod and clasping behavioural tests. Adeno-associated virus-CYP46A1 infection in R6/2 mice also restored levels of cholesterol and lanosterol and increased levels of desmosterol. In vitro, lanosterol and desmosterol were found to protect striatal neurons expressing Exp-HTT from death. We conclude that restoring CYP46A1 activity in the striatum promises a new therapeutic approach in Huntington’s disease.

Journal ArticleDOI
TL;DR: Several of the major avenues that the Shigella research field has taken over the past few years are discussed to gain some insights into the questions that remain surrounding this important human pathogen.
Abstract: Shigella is a pathovar of Escherichia coli comprising four groups, Shigella flexneri, Shigella sonnei, Shigella dysenteriae, and Shigella boydii, each of them, with the exception of S.sonnei, comprising several serotypes. Shigella accounts for the majority of dysentery causing infections occurring world-wide each year. Recent advancements in the Shigella field have led to a better understanding of the molecular mechanisms underlying host epithelial cell invasion and immune cell function manipulation, mainly using S. flexneri as a model. Host-cell invasion is the final step of the infection process, as Shigella's virulence strategy relies also on its ability to survive hostile conditions during its journey through the gastro-intestinal tract, to compete with the host microbiota and to cross the intestinal mucus layer. Hence, the diversity of the virulence strategies among the different Shigella species has not yet been deeply investigated, which might be an important step to understand the epidemiological spreading of Shigella species worldwide and a key aspect for the validation of novel vaccine candidates. The recent development of high-throughput screening and sequencing methods will facilitate these complex comparison studies. In this review we discuss several of the major avenues that the Shigella research field has taken over the past few years and hopefully gain some insights into the questions that remain surrounding this important human pathogen.

Journal ArticleDOI
TL;DR: Overall, it appears that milk or the by-products of milk was an important foodstuff, which may have contributed significantly to the spread of these cultural groups by providing a nourishing and sustainable product for early farming communities.
Abstract: In the absence of any direct evidence, the relative importance of meat and dairy productions to Neolithic prehistoric Mediterranean communities has been extensively debated. Here, we combine lipid residue analysis of ceramic vessels with osteo-archaeological age-at-death analysis from 82 northern Mediterranean and Near Eastern sites dating from the seventh to fifth millennia BC to address this question. The findings show variable intensities in dairy and nondairy activities in the Mediterranean region with the slaughter profiles of domesticated ruminants mirroring the results of the organic residue analyses. The finding of milk residues in very early Neolithic pottery (seventh millennium BC) from both the east and west of the region contrasts with much lower intensities in sites of northern Greece, where pig bones are present in higher frequencies compared with other locations. In this region, the slaughter profiles of all domesticated ruminants suggest meat production predominated. Overall, it appears that milk or the by-products of milk was an important foodstuff, which may have contributed significantly to the spread of these cultural groups by providing a nourishing and sustainable product for early farming communities.

Journal ArticleDOI
TL;DR: In this article, the authors report on the redox mechanisms in high-capacity Li-rich materials Li2Ru1-xMxO3 and Li2Ir1-oxO3 by combining X-ray photoemission spectroscopy (XPS) core peaks and valence intensity analyses.
Abstract: Electrode materials based on Li-rich layered oxides are of growing interest for high-energy Li-ion battery applications because of their staggering capacities associated with the emergence of a novel, reversible anionic process. However, the fundamental science at work behind this new process needs to be well understood for further optimization. Here we report on the redox mechanisms in high-capacity Li-rich materials Li2Ru1–xMxO3 and Li2Ir1–xMxO3, by combining X-ray photoemission spectroscopy (XPS) core peaks and valence intensity analyses. We fully confirm that these materials electrochemically react with Li via cumulative reversible cationic/anionic redox processes, but more importantly we reveal that, depending on the nature of the metal (Ru or Ir), there is a delicate balance between metal and oxygen contributions. For instance, we show a greater implication of oxide ions for Ir-based electrodes, consistent with the higher covalent character of Ir–O bonds compared to Ru–O bonds. We equally provide ev...

Journal ArticleDOI
TL;DR: In this paper, the authors reported the discovery that the known "changing look" AGN Mrk 1018 has changed spectral type for a second time and used spectral fitting to determine the drop in broad line flux and the Balmer decrement.
Abstract: We report the discovery that the known “changing look” AGN Mrk 1018 has changed spectral type for a second time. New VLT-MUSE data taken in 2015 as part of the Close AGN Reference Survey (CARS) shows that the AGN has returned to its original Seyfert 1.9 classification. The CARS sample is selected to contain only bright type 1 AGN, but Mrk 1018’s broad emission lines and continuum, typical of type 1 AGN, have almost entirely disappeared. We use spectral fitting of the MUSE spectrum and previously available spectra to determine the drop in broad line flux and the Balmer decrement. We find that the broad line flux has decreased by a factor of 4.75 ± 0.5 in Hα since an SDSS spectrum was taken in 2000. The Balmer decrement has not changed significantly implying no enhanced reddening with time, but the remaining broad lines are more asymmetric than those present in the type 1 phase. We posit that the change is due to an intrinsic drop in flux from the accretion disk rather than variable extinction or a tidal disruption event

Journal ArticleDOI
TL;DR: The hypothesis that the brain acts as a near-optimal inference device that constantly attempts to infer the time-varying matrix of transition probabilities between the stimuli it receives, even when those stimuli are in fact fully unpredictable is explored.
Abstract: The brain constantly infers the causes of the inputs it receives and uses these inferences to generate statistical expectations about future observations. Experimental evidence for these expectations and their violations include explicit reports, sequential effects on reaction times, and mismatch or surprise signals recorded in electrophysiology and functional MRI. Here, we explore the hypothesis that the brain acts as a near-optimal inference device that constantly attempts to infer the time-varying matrix of transition probabilities between the stimuli it receives, even when those stimuli are in fact fully unpredictable. This parsimonious Bayesian model, with a single free parameter, accounts for a broad range of findings on surprise signals, sequential effects and the perception of randomness. Notably, it explains the pervasive asymmetry between repetitions and alternations encountered in those studies. Our analysis suggests that a neural machinery for inferring transition probabilities lies at the core of human sequence knowledge.

Journal ArticleDOI
TL;DR: Both 3C-based techniques and DNA FISH approaches are discussed to highlight their similarities and differences, the technical biases that affect each approach, and an experimental scheme for comparison of 3C andDNA FISH results are proposed.
Abstract: Chromosome conformation capture (3C)-based techniques have revolutionized the field of nuclear organization, partly replacing DNA FISH as the method of choice for studying three-dimensional chromosome architecture. Although DNA FISH is commonly used for confirming 3C-based findings, the two techniques are conceptually and technically different and comparing their results is not trivial. Here, we discuss both 3C-based techniques and DNA FISH approaches to highlight their similarities and differences. We then describe the technical biases that affect each approach, and review the available reports that address their compatibility. Finally, we propose an experimental scheme for comparison of 3C and DNA FISH results.

Journal ArticleDOI
24 Nov 2016-Nature
TL;DR: It is shown that, in the African striped mouse (Rhabdomys pumilio), periodic dorsal stripes result from underlying differences in melanocyte maturation, which give rise to spatial variation in hair colour.
Abstract: Mammalian colour patterns are among the most recognizable characteristics found in nature and can have a profound impact on fitness. However, little is known about the mechanisms underlying the formation and subsequent evolution of these patterns. Here we show that, in the African striped mouse (Rhabdomys pumilio), periodic dorsal stripes result from underlying differences in melanocyte maturation, which give rise to spatial variation in hair colour. We identify the transcription factor ALX3 as a regulator of this process. In embryonic dorsal skin, patterned expression of Alx3 precedes pigment stripes and acts to directly repress Mitf, a master regulator of melanocyte differentiation, thereby giving rise to light-coloured hair. Moreover, Alx3 is upregulated in the light stripes of chipmunks, which have independently evolved a similar dorsal pattern. Our results show a previously undescribed mechanism for modulating spatial variation in hair colour and provide insights into how phenotypic novelty evolves. Alx3-induced modulation of Mitf expression alters melanocyte differentiation and gives rise to the hair colour differences underlying the repeated evolution of dorsal stripes in rodents. Mammalian colour patterns are more than skin deep. They can reveal much about underlying development, and can be crucial for fitness. But how are they made? Hopi Hoekstra and colleagues examine the development of stripes in the African striped mouse (Rhabdomys pumilio) and identify that the transcription factor Alx3 is a regulator of differential rates of pigment-cell maturation that give rise to stripiness. Even in embryonic life, patterned expression of Alx3 foreshadows the stripes that will eventually develop. Alx3 also represses Mitf, a master regulator of melanocyte differentiation, giving rise to light-colored hair. It's not just stripey mice, however: Alx3 is also upregulated in the light stripes of chipmunks, which have independently evolved a similar dorsal coat pattern, revealing a common basis for patterning in rodents.