Showing papers in "Nature Communications in 2016"

Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

Abstract: Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research.

Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs

Abstract: Circular RNAs (circRNAs) represent a class of widespread and diverse endogenous RNAs that may regulate gene expression in eukaryotes. However, the regulation and function of human circRNAs remain largely unknown. Here we generate ribosomal-depleted RNA sequencing data from six normal tissues and seven cancers, and detect at least 27,000 circRNA candidates. Many of these circRNAs are differently expressed between the normal and cancerous tissues. We further characterize one abundant circRNA derived from Exon2 of the HIPK3 gene, termed circHIPK3. The silencing of circHIPK3 but not HIPK3 mRNA significantly inhibits human cell growth. Via a luciferase screening assay, circHIPK3 is observed to sponge to 9 miRNAs with 18 potential binding sites. Specifically, we show that circHIPK3 directly binds to miR-124 and inhibits miR-124 activity. Our results provide evidence that circular RNA produced from precursor mRNA may have a regulatory role in human cells.

Negative magnetoresistance without well-defined chirality in the Weyl semimetal TaP

Abstract: Weyl semimetals (WSMs) are topological quantum states wherein the electronic bands disperse linearly around pairs of nodes with fixed chirality, the Weyl points In WSMs, nonorthogonal electric and magnetic fields induce an exotic phenomenon known as the chiral anomaly, resulting in an unconventional negative longitudinal magnetoresistance, the chiral-magnetic effect However, it remains an open question to which extent this effect survives when chirality is not well-defined Here, we establish the detailed Fermi-surface topology of the recently identified WSM TaP via combined angle-resolved quantum-oscillation spectra and band-structure calculations The Fermi surface forms banana-shaped electron and hole pockets surrounding pairs of Weyl points Although this means that chirality is ill-defined in TaP, we observe a large negative longitudinal magnetoresistance We show that the magnetoresistance can be affected by a magnetic field-induced inhomogeneous current distribution inside the sample

Platinum single-atom and cluster catalysis of the hydrogen evolution reaction

Abstract: Platinum-based catalysts have been considered the most effective electrocatalysts for the hydrogen evolution reaction in water splitting. However, platinum utilization in these electrocatalysts is extremely low, as the active sites are only located on the surface of the catalyst particles. Downsizing catalyst nanoparticles to single atoms is highly desirable to maximize their efficiency by utilizing nearly all platinum atoms. Here we report on a practical synthesis method to produce isolated single platinum atoms and clusters using the atomic layer deposition technique. The single platinum atom catalysts are investigated for the hydrogen evolution reaction, where they exhibit significantly enhanced catalytic activity (up to 37 times) and high stability in comparison with the state-of-the-art commercial platinum/carbon catalysts. The X-ray absorption fine structure and density functional theory analyses indicate that the partially unoccupied density of states of the platinum atoms’ 5d orbitals on the nitrogen-doped graphene are responsible for the excellent performance. Downsizing platinum based nanocatalysts has the twin advantages of lower platinum usage and increased activity per platinum atom. Here, the authors report an atomic layer deposition technique for single platinum atom catalyst fabrication and assess their hydrogen evolution activity.

The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes

Abstract: The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.

Multidimensional materials and device architectures for future hybrid energy storage

Abstract: Electrical energy storage plays a vital role in daily life due to our dependence on numerous portable electronic devices. Moreover, with the continued miniaturization of electronics, integration of wireless devices into our homes and clothes and the widely anticipated ‘Internet of Things', there are intensive efforts to develop miniature yet powerful electrical energy storage devices. This review addresses the cutting edge of electrical energy storage technology, outlining approaches to overcome current limitations and providing future research directions towards the next generation of electrical energy storage devices whose characteristics represent a true hybridization of batteries and electrochemical capacitors.

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

Abstract: A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

Array of nanosheets render ultrafast and high-capacity Na-ion storage by tunable pseudocapacitance

Abstract: Sodium-ion batteries are a potentially low-cost and safe alternative to the prevailing lithium-ion battery technology. However, it is a great challenge to achieve fast charging and high power density for most sodium-ion electrodes because of the sluggish sodiation kinetics. Here we demonstrate a high-capacity and high-rate sodium-ion anode based on ultrathin layered tin(II) sulfide nanostructures, in which a maximized extrinsic pseudocapacitance contribution is identified and verified by kinetics analysis. The graphene foam supported tin(II) sulfide nanoarray anode delivers a high reversible capacity of ∼1,100 mAh g(-1) at 30 mA g(-1) and ∼420 mAh g(-1) at 30 A g(-1), which even outperforms its lithium-ion storage performance. The surface-dominated redox reaction rendered by our tailored ultrathin tin(II) sulfide nanostructures may also work in other layered materials for high-performance sodium-ion storage.

Fast and sensitive taxonomic classification for metagenomics with Kaiju

Abstract: Metagenomics emerged as an important field of research not only in microbial ecology but also for human health and disease, and metagenomic studies are performed on increasingly larger scales. While recent taxonomic classification programs achieve high speed by comparing genomic k-mers, they often lack sensitivity for overcoming evolutionary divergence, so that large fractions of the metagenomic reads remain unclassified. Here we present the novel metagenome classifier Kaiju, which finds maximum (in-)exact matches on the protein-level using the Burrows–Wheeler transform. We show in a genome exclusion benchmark that Kaiju classifies reads with higher sensitivity and similar precision compared with current k-mer-based classifiers, especially in genera that are underrepresented in reference databases. We also demonstrate that Kaiju classifies up to 10 times more reads in real metagenomes. Kaiju can process millions of reads per minute and can run on a standard PC. Source code and web server are available at http://kaiju.binf.ku.dk . Here, Anders Krogh and colleagues describe Kaiju, a metagenome taxonomic classification program that uses maximum (in-)exact matches on the protein-level to account for evolutionary divergence. The authors show that Kaiju performs faster and is more sensitive compared with existing algorithms and can be used on a standard computer.

Microbial diversity drives multifunctionality in terrestrial ecosystems

Abstract: Despite the importance of microbial communities for ecosystem services and human welfare, the relationship between microbial diversity and multiple ecosystem functions and services (that is, multifunctionality) at the global scale has yet to be evaluated. Here we use two independent, large-scale databases with contrasting geographic coverage (from 78 global drylands and from 179 locations across Scotland, respectively), and report that soil microbial diversity positively relates to multifunctionality in terrestrial ecosystems. The direct positive effects of microbial diversity were maintained even when accounting simultaneously for multiple multifunctionality drivers (climate, soil abiotic factors and spatial predictors). Our findings provide empirical evidence that any loss in microbial diversity will likely reduce multifunctionality, negatively impacting the provision of services such as climate regulation, soil fertility and food and fibre production by terrestrial ecosystems.

Exceptional damage-tolerance of a medium-entropy alloy CrCoNi at cryogenic temperatures

Abstract: High-entropy alloys are an intriguing new class of metallic materials that derive their properties from being multi-element systems that can crystallize as a single phase, despite containing high concentrations of five or more elements with different crystal structures. Here we examine an equiatomic medium-entropy alloy containing only three elements, CrCoNi, as a single-phase face-centred cubic solid solution, which displays strength-toughness properties that exceed those of all high-entropy alloys and most multi-phase alloys. At room temperature, the alloy shows tensile strengths of almost 1 GPa, failure strains of ∼70% and KJIc fracture-toughness values above 200 MPa m(1/2); at cryogenic temperatures strength, ductility and toughness of the CrCoNi alloy improve to strength levels above 1.3 GPa, failure strains up to 90% and KJIc values of 275 MPa m(1/2). Such properties appear to result from continuous steady strain hardening, which acts to suppress plastic instability, resulting from pronounced dislocation activity and deformation-induced nano-twinning.

Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints.

Abstract: Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.

Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription

Abstract: Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. Chromatin immunoprecipitation (ChIP)-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2-binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.

Balancing surface adsorption and diffusion of lithium-polysulfides on nonconductive oxides for lithium-sulfur battery design.

Abstract: Lithium-sulfur batteries have attracted attention due to their six-fold specific energy compared with conventional lithium-ion batteries. Dissolution of lithium polysulfides, volume expansion of sulfur and uncontrollable deposition of lithium sulfide are three of the main challenges for this technology. State-of-the-art sulfur cathodes based on metal-oxide nanostructures can suppress the shuttle-effect and enable controlled lithium sulfide deposition. However, a clear mechanistic understanding and corresponding selection criteria for the oxides are still lacking. Herein, various nonconductive metal-oxide nanoparticle-decorated carbon flakes are synthesized via a facile biotemplating method. The cathodes based on magnesium oxide, cerium oxide and lanthanum oxide show enhanced cycling performance. Adsorption experiments and theoretical calculations reveal that polysulfide capture by the oxides is via monolayered chemisorption. Moreover, we show that better surface diffusion leads to higher deposition efficiency of sulfide species on electrodes. Hence, oxide selection is proposed to balance optimization between sulfide-adsorption and diffusion on the oxides.

Sixteen years of change in the global terrestrial human footprint and implications for biodiversity conservation

Abstract: Human pressures on the environment are changing spatially and temporally, with profound implications for the planet’s biodiversity and human economies. Here we use recently available data on infrastructure, land cover and human access into natural areas to construct a globally standardized measure of the cumulative human footprint on the terrestrial environment at 1 km2 resolution from 1993 to 2009. We note that while the human population has increased by 23% and the world economy has grown 153%, the human footprint has increased by just 9%. Still, 75% the planet’s land surface is experiencing measurable human pressures. Moreover, pressures are perversely intense, widespread and rapidly intensifying in places with high biodiversity. Encouragingly, we discover decreases in environmental pressures in the wealthiest countries and those with strong control of corruption. Clearly the human footprint on Earth is changing, yet there are still opportunities for conservation gains. Habitat loss and urbanization are primary components of human impact on the environment. Here, Venter et al.use global data on infrastructure, agriculture, and urbanization to show that the human footprint is growing slower than the human population, but footprints are increasing in biodiverse regions.

High-efficiency and air-stable P3HT-based polymer solar cells with a new non-fullerene acceptor

Abstract: Solution-processed organic photovoltaics (OPV) offer the attractive prospect of low-cost, light-weight and environmentally benign solar energy production. The highest efficiency OPV at present use low-bandgap donor polymers, many of which suffer from problems with stability and synthetic scalability. They also rely on fullerene-based acceptors, which themselves have issues with cost, stability and limited spectral absorption. Here we present a new non-fullerene acceptor that has been specifically designed to give improved performance alongside the wide bandgap donor poly(3-hexylthiophene), a polymer with significantly better prospects for commercial OPV due to its relative scalability and stability. Thanks to the well-matched optoelectronic and morphological properties of these materials, efficiencies of 6.4% are achieved which is the highest reported for fullerene-free P3HT devices. In addition, dramatically improved air stability is demonstrated relative to other high-efficiency OPV, showing the excellent potential of this new material combination for future technological applications.

Bifunctional non-noble metal oxide/chalcogenide nanoparticle electrocatalysts through lithium-induced conversion for overall water-splitting

Abstract: Described here is a method for improving the catalytic activity of an electrocatalyst, comprising subjecting the electrocatalyst to 1-10 galvanostatic lithiation/delithiation cycles, wherein the electrocatalyst comprises at least one transition metal oxide (TMO) or transition metal chalcogenide (TMC). Also described here is an electrocatalyst and a water-splitting device comprising the electrocatalyst.

Electron–phonon coupling in hybrid lead halide perovskites

Abstract: Phonon scattering limits charge-carrier mobilities and governs emission line broadening in hybrid metal halide perovskites. Establishing how charge carriers interact with phonons in these materials is therefore essential for the development of high-efficiency perovskite photovoltaics and low-cost lasers. Here we investigate the temperature dependence of emission line broadening in the four commonly studied formamidinium and methylammonium perovskites, HC(NH2)2PbI3, HC(NH2)2PbBr3, CH3NH3PbI3 and CH3NH3PbBr3, and discover that scattering from longitudinal optical phonons via the Frohlich interaction is the dominant source of electron–phonon coupling near room temperature, with scattering off acoustic phonons negligible. We determine energies for the interacting longitudinal optical phonon modes to be 11.5 and 15.3 meV, and Frohlich coupling constants of ∼40 and 60 meV for the lead iodide and bromide perovskites, respectively. Our findings correlate well with first-principles calculations based on many-body perturbation theory, which underlines the suitability of an electronic band-structure picture for describing charge carriers in hybrid perovskites. Phonon scattering limits charge transport in perovskite solar cells, yet the interactions involved are still poorly understood. Here, Wright et al. show by photoluminescence measurements and first-principles calculations that longitudinal optical phonons dominate the electron-phonon coupling at room temperature.

Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling

Abstract: The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity.

11.4% Efficiency non-fullerene polymer solar cells with trialkylsilyl substituted 2D-conjugated polymer as donor.

Abstract: Simutaneously high open circuit voltage and high short circuit current density is a big challenge for achieving high efficiency polymer solar cells due to the excitonic nature of organic semdonductors. Herein, we developed a trialkylsilyl substituted 2D-conjugated polymer with the highest occupied molecular orbital level down-shifted by Si–C bond interaction. The polymer solar cells obtained by pairing this polymer with a non-fullerene acceptor demonstrated a high power conversion efficiency of 11.41% with both high open circuit voltage of 0.94 V and high short circuit current density of 17.32 mA cm−2 benefitted from the complementary absorption of the donor and acceptor, and the high hole transfer efficiency from acceptor to donor although the highest occupied molecular orbital level difference between the donor and acceptor is only 0.11 eV. The results indicate that the alkylsilyl substitution is an effective way in designing high performance conjugated polymer photovoltaic materials. In organic photovoltaics, non-fullerene acceptors relax matching rules and allow for the development of new donor polymers. Here, Bin et al. design a donor polymer and obtain high photoconversion efficiencies despite the low energy offset for hole transfer between the acceptor and the donor.

Catch reconstructions reveal that global marine fisheries catches are higher than reported and declining

Abstract: Fisheries data assembled by the Food and Agriculture Organization (FAO) suggest that global marine fisheries catches increased to 86 million tonnes in 1996, then slightly declined. Here, using a decade-long multinational ‘catch reconstruction' project covering the Exclusive Economic Zones of the world's maritime countries and the High Seas from 1950 to 2010, and accounting for all fisheries, we identify catch trajectories differing considerably from the national data submitted to the FAO. We suggest that catch actually peaked at 130 million tonnes, and has been declining much more strongly since. This decline in reconstructed catches reflects declines in industrial catches and to a smaller extent declining discards, despite industrial fishing having expanded from industrialized countries to the waters of developing countries. The differing trajectories documented here suggest a need for improved monitoring of all fisheries, including often neglected small-scale fisheries, and illegal and other problematic fisheries, as well as discarded bycatch.

YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex.

Abstract: Methylation at the N6 position of adenosine (m(6)A) is the most abundant RNA modification within protein-coding and long noncoding RNAs in eukaryotes and is a reversible process with important biological functions. YT521-B homology domain family (YTHDF) proteins are the readers of m(6)A, the binding of which results in the alteration of the translation efficiency and stability of m(6)A-containing RNAs. However, the mechanism by which YTHDF proteins cause the degradation of m(6)A-containing RNAs is poorly understood. Here we report that m(6)A-containing RNAs exhibit accelerated deadenylation that is mediated by the CCR4-NOT deadenylase complex. We further show that YTHDF2 recruits the CCR4-NOT complex through a direct interaction between the YTHDF2 N-terminal region and the SH domain of the CNOT1 subunit, and that this recruitment is essential for the deadenylation of m(6)A-containing RNAs by CAF1 and CCR4. Therefore, we have uncovered the mechanism of YTHDF2-mediated degradation of m(6)A-containing RNAs in mammalian cells.

Alterations of the human gut microbiome in multiple sclerosis

Abstract: The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.

Highly selective plasma-activated copper catalysts for carbon dioxide reduction to ethylene

Abstract: There is an urgent need to develop technologies that use renewable energy to convert waste products such as carbon dioxide into hydrocarbon fuels. Carbon dioxide can be electrochemically reduced to hydrocarbons over copper catalysts, although higher efficiency is required. We have developed oxidized copper catalysts displaying lower overpotentials for carbon dioxide electroreduction and record selectivity towards ethylene (60%) through facile and tunable plasma treatments. Herein we provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. Operando X-ray absorption spectroscopy and cross-sectional scanning transmission electron microscopy show that copper oxides are surprisingly resistant to reduction and copper(+) species remain on the surface during the reaction. Our results demonstrate that the roughness of oxide-derived copper catalysts plays only a partial role in determining the catalytic performance, while the presence of copper(+) is key for lowering the onset potential and enhancing ethylene selectivity.

Direct evidence for microbial-derived soil organic matter formation and its ecophysiological controls

Abstract: Soil organic matter (SOM) and the carbon and nutrients therein drive fundamental submicron- to global-scale biogeochemical processes and influence carbon-climate feedbacks. Consensus is emerging that microbial materials are an important constituent of stable SOM, and new conceptual and quantitative SOM models are rapidly incorporating this view. However, direct evidence demonstrating that microbial residues account for the chemistry, stability and abundance of SOM is still lacking. Further, emerging models emphasize the stabilization of microbial-derived SOM by abiotic mechanisms, while the effects of microbial physiology on microbial residue production remain unclear. Here we provide the first direct evidence that soil microbes produce chemically diverse, stable SOM. We show that SOM accumulation is driven by distinct microbial communities more so than clay mineralogy, where microbial-derived SOM accumulation is greatest in soils with higher fungal abundances and more efficient microbial biomass production. Soil microbes process plant remnants and are hypothesized to synthesize soil organic matter (SOM). Here, Kallenbach and colleagues directly measure chemically diverse and stable SOM derived from microbial communities in the absence of plant compounds.

Thousands of microbial genomes shed light on interconnected biogeochemical processes in an aquifer system

Abstract: The subterranean world hosts up to one-fifth of all biomass, including microbial communities that drive transformations central to Earth’s biogeochemical cycles. However, little is known about how complex microbial communities in such environments are structured, and how inter-organism interactions shape ecosystem function. Here we apply terabase-scale cultivation-independent metagenomics to aquifer sediments and groundwater, and reconstruct 2,540 draft-quality, near-complete and complete strain-resolved genomes that represent the majority of known bacterial phyla as well as 47 newly discovered phylum-level lineages. Metabolic analyses spanning this vast phylogenetic diversity and representing up to 36% of organisms detected in the system are used to document the distribution of pathways in coexisting organisms. Consistent with prior findings indicating metabolic handoffs in simple consortia, we find that few organisms within the community can conduct multiple sequential redox transformations. As environmental conditions change, different assemblages of organisms are selected for, altering linkages among the major biogeochemical cycles. Microorganisms from the terrestrial subsurface are understudied. Here, Anantharamanet al. analyse aquifer sediments and groundwater by genome-resolved metagenomics and reconstruct 2,540 genomes representing the majority of known bacterial phyla as well as 47 new phylum-level lineages.

Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans.

Abstract: Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their molecular mechanism in human disease remains obscure. Here we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers atheroprotection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. CircANRIL binds to pescadillo homologue 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key cell functions in atherosclerosis. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring atheroprotection, thereby showing that circularization of long non-coding RNAs may alter RNA function and protect from human disease.

Coupled molybdenum carbide and reduced graphene oxide electrocatalysts for efficient hydrogen evolution

Abstract: Electrochemical water splitting is one of the most economical and sustainable methods for large-scale hydrogen production. However, the development of low-cost and earth-abundant non-noble-metal catalysts for the hydrogen evolution reaction remains a challenge. Here we report a two-dimensional coupled hybrid of molybdenum carbide and reduced graphene oxide with a ternary polyoxometalate-polypyrrole/reduced graphene oxide nanocomposite as a precursor. The hybrid exhibits outstanding electrocatalytic activity for the hydrogen evolution reaction and excellent stability in acidic media, which is, to the best of our knowledge, the best among these reported non-noble-metal catalysts. Theoretical calculations on the basis of density functional theory reveal that the active sites for hydrogen evolution stem from the pyridinic nitrogens, as well as the carbon atoms, in the graphene. In a proof-of-concept trial, an electrocatalyst for hydrogen evolution is fabricated, which may open new avenues for the design of nanomaterials utilizing POMs/conducting polymer/reduced-graphene oxide nanocomposites.

Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis

Abstract: Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

Nickel–vanadium monolayer double hydroxide for efficient electrochemical water oxidation

Abstract: Highly active and low-cost electrocatalysts for water oxidation are required due to the demands on sustainable solar fuels; however, developing highly efficient catalysts to meet industrial require ...