Showing papers by "Spanish National Research Council published in 2018"

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Abstract: Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Planck 2018 results. VI. Cosmological parameters

Abstract: We present cosmological parameter results from the final full-mission Planck measurements of the CMB anisotropies. We find good consistency with the standard spatially-flat 6-parameter $\Lambda$CDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted "base $\Lambda$CDM" in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density $\Omega_c h^2 = 0.120\pm 0.001$, baryon density $\Omega_b h^2 = 0.0224\pm 0.0001$, scalar spectral index $n_s = 0.965\pm 0.004$, and optical depth $\tau = 0.054\pm 0.007$ (in this abstract we quote $68\,\%$ confidence regions on measured parameters and $95\,\%$ on upper limits). The angular acoustic scale is measured to $0.03\,\%$ precision, with $100\theta_*=1.0411\pm 0.0003$. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-$\Lambda$CDM cosmology, the inferred late-Universe parameters are: Hubble constant $H_0 = (67.4\pm 0.5)$km/s/Mpc; matter density parameter $\Omega_m = 0.315\pm 0.007$; and matter fluctuation amplitude $\sigma_8 = 0.811\pm 0.006$. We find no compelling evidence for extensions to the base-$\Lambda$CDM model. Combining with BAO we constrain the effective extra relativistic degrees of freedom to be $N_{\rm eff} = 2.99\pm 0.17$, and the neutrino mass is tightly constrained to $\sum m_ u< 0.12$eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base -$\Lambda$CDM at over $2\,\sigma$, which pulls some parameters that affect the lensing amplitude away from the base-$\Lambda$CDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. (Abridged)

Binary Companions of Evolved Stars in APOGEE DR14: Search Method and Catalog of ∼5000 Companions

Abstract: Multi-epoch radial velocity measurements of stars can be used to identify stellar, sub-stellar, and planetary-mass companions. Even a small number of observation epochs can be informative about companions, though there can be multiple qualitatively different orbital solutions that fit the data. We have custom-built a Monte Carlo sampler (The Joker) that delivers reliable (and often highly multi-modal) posterior samplings for companion orbital parameters given sparse radial-velocity data. Here we use The Joker to perform a search for companions to 96,231 red-giant stars observed in the APOGEE survey (DR14) with $\\geq 3$ spectroscopic epochs. We select stars with probable companions by making a cut on our posterior belief about the amplitude of the stellar radial-velocity variation induced by the orbit. We provide (1) a catalog of 320 companions for which the stellar companion properties can be confidently determined, (2) a catalog of 4,898 stars that likely have companions, but would require more observations to uniquely determine the orbital properties, and (3) posterior samplings for the full orbital parameters for all stars in the parent sample. We show the characteristics of systems with confidently determined companion properties and highlight interesting systems with candidate compact object companions.

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Abstract: An annotated reference sequence representing the hexaploid bread wheat genome in 21 pseudomolecules has been analyzed to identify the distribution and genomic context of coding and noncoding elements across the A, B, and D subgenomes. With an estimated coverage of 94% of the genome and containing 107,891 high-confidence gene models, this assembly enabled the discovery of tissue- and developmental stage-related coexpression networks by providing a transcriptome atlas representing major stages of wheat development. Dynamics of complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. This community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.

Analysis of shared heritability in common disorders of the brain

Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

EMT in cancer

Abstract: Similar to embryonic development, changes in cell phenotypes defined as an epithelial to mesenchymal transition (EMT) have been shown to play a role in the tumorigenic process. Although the first description of EMT in cancer was in cell cultures, evidence for its role in vivo is now widely reported but also actively debated. Moreover, current research has exemplified just how complex this phenomenon is in cancer, leaving many exciting, open questions for researchers to answer in the future. With these points in mind, we asked four scientists for their opinions on the role of EMT in cancer and the challenges faced by scientists working in this fast-moving field.

Towards flexible solid-state supercapacitors for smart and wearable electronics

Abstract: Flexible solid-state supercapacitors (FSSCs) are frontrunners in energy storage device technology and have attracted extensive attention owing to recent significant breakthroughs in modern wearable electronics In this study, we review the state-of-the-art advancements in FSSCs to provide new insights on mechanisms, emerging electrode materials, flexible gel electrolytes and novel cell designs The review begins with a brief introduction on the fundamental understanding of charge storage mechanisms based on the structural properties of electrode materials The next sections briefly summarise the latest progress in flexible electrodes (ie, freestanding and substrate-supported, including textile, paper, metal foil/wire and polymer-based substrates) and flexible gel electrolytes (ie, aqueous, organic, ionic liquids and redox-active gels) Subsequently, a comprehensive summary of FSSC cell designs introduces some emerging electrode materials, including MXenes, metal nitrides, metal–organic frameworks (MOFs), polyoxometalates (POMs) and black phosphorus Some potential practical applications, such as the development of piezoelectric, photo-, shape-memory, self-healing, electrochromic and integrated sensor-supercapacitors are also discussed The final section highlights current challenges and future perspectives on research in this thriving field

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

Abstract: The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.

Prospects for Observing and Localizing Gravitational-Wave Transients with Advanced LIGO, Advanced Virgo and KAGRA

Abstract: We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5– 20 deg2 requires at least three detectors of sensitivity within a factor of ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

Plasmon induced thermoelectric effect in graphene

Abstract: Graphene has emerged as a promising material for optoelectronics due to its potential for ultrafast and broad-band photodetection. The photoresponse of graphene junctions is characterized by two competing photocurrent generation mechanisms: a conventional photovoltaic effect and a more dominant hot-carrier-assisted photothermoelectric (PTE) effect. The PTE effect is understood to rely on variations in the Seebeck coefficient through the graphene doping profile. A second PTE effect can occur across a homogeneous graphene channel in the presence of an electronic temperature gradient. Here, we study the latter effect facilitated by strongly localised plasmonic heating of graphene carriers in the presence of nanostructured electrical contacts resulting in electronic temperatures of the order of 2000 K. At certain conditions, the plasmon-induced PTE photocurrent contribution can be isolated. In this regime, the device effectively operates as a sensitive electronic thermometer and as such represents an enabling technology for development of hot carrier based plasmonic devices.

Climate change and interconnected risks to sustainable development in the Mediterranean

Abstract: Recent accelerated climate change has exacerbated existing environmental problems in the Mediterranean Basin that are caused by the combination of changes in land use, increasing pollution and declining biodiversity. For five broad and interconnected impact domains (water, ecosystems, food, health and security), current change and future scenarios consistently point to significant and increasing risks during the coming decades. Policies for the sustainable development of Mediterranean countries need to mitigate these risks and consider adaptation options, but currently lack adequate information — particularly for the most vulnerable southern Mediterranean societies, where fewer systematic observations schemes and impact models are based. A dedicated effort to synthesize existing scientific knowledge across disciplines is underway and aims to provide a better understanding of the combined risks posed.

Gaia Data Release 2. Observations of solar system objects

Abstract: Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ~ 12 − 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ~ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.

Gaia Data Release 2. Kinematics of globular clusters and dwarf galaxies around the Milky Way

Abstract: Context. Aims: The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods: Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results: Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (iv) derive a lower limit for the mass of the Milky Way of 9.1-2.6+6.2 × 1011 M⊙ based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (vi) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions: All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.

Recent Progress and Perspective in Electrode Materials for K-Ion Batteries

Abstract: Author(s): Kim, H; Kim, JC; Bianchini, M; Seo, DH; Rodriguez-Garcia, J; Ceder, G | Abstract: The development of rechargeable batteries using K ions as charge carriers has recently attracted considerable attention in the search for cost-effective and large-scale energy storage systems. In light of this trend, various materials for positive and negative electrodes are proposed and evaluated for application in K-ion batteries. Here, a comprehensive review of ongoing materials research on nonaqueous K-ion batteries is offered. Information on the status of new materials discovery and insights to help understand the K-storage mechanisms are provided. In addition, strategies to enhance the electrochemical properties of K-ion batteries and computational approaches to better understand their thermodynamic properties are included. Finally, K-ion batteries are compared to competing Li and Na systems and pragmatic opportunities and future research directions are discussed.

GANimation: anatomically-aware facial animation from a single image

Abstract: Recent advances in Generative Adversarial Networks (GANs) have shown impressive results for task of facial expression synthesis. The most successful architecture is StarGAN, that conditions GANs’ generation process with images of a specific domain, namely a set of images of persons sharing the same expression. While effective, this approach can only generate a discrete number of expressions, determined by the content of the dataset. To address this limitation, in this paper, we introduce a novel GAN conditioning scheme based on Action Units (AU) annotations, which describes in a continuous manifold the anatomical facial movements defining a human expression. Our approach allows controlling the magnitude of activation of each AU and combine several of them. Additionally, we propose a fully unsupervised strategy to train the model, that only requires images annotated with their activated AUs, and exploit attention mechanisms that make our network robust to changing backgrounds and lighting conditions. Extensive evaluation show that our approach goes beyond competing conditional generators both in the capability to synthesize a much wider range of expressions ruled by anatomically feasible muscle movements, as in the capacity of dealing with images in the wild.

An inverse latitudinal gradient in speciation rate for marine fishes

Abstract: Far more species of organisms are found in the tropics than in temperate and polar regions, but the evolutionary and ecological causes of this pattern remain controversial1,2. Tropical marine fish communities are much more diverse than cold-water fish communities found at higher latitudes3,4, and several explanations for this latitudinal diversity gradient propose that warm reef environments serve as evolutionary ‘hotspots’ for species formation5–8. Here we test the relationship between latitude, species richness and speciation rate across marine fishes. We assembled a time-calibrated phylogeny of all ray-finned fishes (31,526 tips, of which 11,638 had genetic data) and used this framework to describe the spatial dynamics of speciation in the marine realm. We show that the fastest rates of speciation occur in species-poor regions outside the tropics, and that high-latitude fish lineages form new species at much faster rates than their tropical counterparts. High rates of speciation occur in geographical regions that are characterized by low surface temperatures and high endemism. Our results reject a broad class of mechanisms under which the tropics serve as an evolutionary cradle for marine fish diversity and raise new questions about why the coldest oceans on Earth are present-day hotspots of species formation.

Accelerated increase in plant species richness on mountain summits is linked to warming

Abstract: Globally accelerating trends in societal development and human environmental impacts since the mid-twentieth century 1–7 are known as the Great Acceleration and have been discussed as a key indicator of the onset of the Anthropocene epoch 6 . While reports on ecological responses (for example, changes in species range or local extinctions) to the Great Acceleration are multiplying 8, 9 , it is unknown whether such biotic responses are undergoing a similar acceleration over time. This knowledge gap stems from the limited availability of time series data on biodiversity changes across large temporal and geographical extents. Here we use a dataset of repeated plant surveys from 302 mountain summits across Europe, spanning 145 years of observation, to assess the temporal trajectory of mountain biodiversity changes as a globally coherent imprint of the Anthropocene. We find a continent-wide acceleration in the rate of increase in plant species richness, with five times as much species enrichment between 2007 and 2016 as fifty years ago, between 1957 and 1966. This acceleration is strikingly synchronized with accelerated global warming and is not linked to alternative global change drivers. The accelerating increases in species richness on mountain summits across this broad spatial extent demonstrate that acceleration in climate-induced biotic change is occurring even in remote places on Earth, with potentially far-ranging consequences not only for biodiversity, but also for ecosystem functioning and services.

The dark energy survey data release 1

Abstract: We describe the first public data release of the Dark Energy Survey, DES DR1, consisting of reduced single-epoch images, co-added images, co-added source catalogs, and associated products and services assembled over the first 3 yr of DES science operations. DES DR1 is based on optical/near-infrared imaging from 345 distinct nights (2013 August to 2016 February) by the Dark Energy Camera mounted on the 4 m Blanco telescope at the Cerro Tololo InterAmerican Observatory in Chile. We release data from the DES wide-area survey covering similar to 5000 deg(2) of the southern Galactic cap in five broad photometric bands, grizY. DES DR1 has a median delivered point-spread function of g = 1.12, r = 0.96, i = 0.88, z = 0.84, and Y = 0.'' 90 FWHM, a photometric precision of <1% in all bands, and an astrometric precision of 151 mas. The median co-added catalog depth for a 1.'' 95 diameter aperture at signal-to-noise ratio (S/N) = 10 is g = 24.33, r = 24.08, i = 23.44, z = 22.69, and Y = 21.44 mag. DES DR1 includes nearly 400 million distinct astronomical objects detected in similar to 10,000 co-add tiles of size 0.534 deg(2) produced from similar to 39,000 individual exposures. Benchmark galaxy and stellar samples contain similar to 310 million and similar to 80 million objects, respectively, following a basic object quality selection. These data are accessible through a range of interfaces, including query web clients, image cutout servers, jupyter notebooks, and an interactive co-add image visualization tool. DES DR1 constitutes the largest photometric data set to date at the achieved depth and photometric precision.

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression

Abstract: Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease.

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae.

Abstract: Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole These drugs might be considered in some specific situations AmpC producers are resistant to cephamycins, but cefepime is an option In the case of carbapenemase-producing Enterobacteriaceae (CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient

Enhancer redundancy provides phenotypic robustness in mammalian development

Abstract: Distant-acting tissue-specific enhancers, which regulate gene expression, vastly outnumber protein-coding genes in mammalian genomes, but the functional importance of this regulatory complexity remains unclear Here we show that the pervasive presence of multiple enhancers with similar activities near the same gene confers phenotypic robustness to loss-of-function mutations in individual enhancers We used genome editing to create 23 mouse deletion lines and inter-crosses, including both single and combinatorial enhancer deletions at seven distinct loci required for limb development Unexpectedly, none of the ten deletions of individual enhancers caused noticeable changes in limb morphology By contrast, the removal of pairs of limb enhancers near the same gene resulted in discernible phenotypes, indicating that enhancers function redundantly in establishing normal morphology In a genetic background sensitized by reduced baseline expression of the target gene, even single enhancer deletions caused limb abnormalities, suggesting that functional redundancy is conferred by additive effects of enhancers on gene expression levels A genome-wide analysis integrating epigenomic and transcriptomic data from 29 developmental mouse tissues revealed that mammalian genes are very commonly associated with multiple enhancers that have similar spatiotemporal activity Systematic exploration of three representative developmental structures (limb, brain and heart) uncovered more than one thousand cases in which five or more enhancers with redundant activity patterns were found near the same gene Together, our data indicate that enhancer redundancy is a remarkably widespread feature of mammalian genomes that provides an effective regulatory buffer to prevent deleterious phenotypic consequences upon the loss of individual enhancers

Conceptual and statistical problems with the DEC+J model of founder‐event speciation and its comparison with DEC via model selection

Abstract: Phylogenetic studies of geographic range evolution are increasingly using statistical model selection methods to choose among variants of the dispersal-extinction-cladogenesis (DEC) model, especially between DEC and DEC+J, a variant that emphasizes “jump dispersal,” or founder-event speciation, as a type of cladogenetic range inheritance scenario. Unfortunately, DEC+J is a poor model of founder-event speciation, and statistical comparisons of its likelihood with DEC are inappropriate. DEC and DEC+J share a conceptual flaw: cladogenetic events of range inheritance at ancestral nodes, unlike anagenetic events of dispersal and local extinction along branches, are not modelled as being probabilistic with respect to time. Ignoring this probability factor artificially inflates the contribution of cladogenetic events to the likelihood, and leads to underestimates of anagenetic, time-dependent range evolution. The flaw is exacerbated in DEC+J because not only is jump dispersal allowed, expanding the set of cladogenetic events, its probability relative to non-jump events is assigned a free parameter, j, that when maximized precludes the possibility of non-jump events at ancestral nodes. DEC+J thus parameterizes the mode of speciation, but like DEC, it does not parameterize the rate of speciation. This inconsistency has undesirable consequences, such as a greater tendency towards degenerate inferences in which the data are explained entirely by cladogenetic events (at which point branch lengths become irrelevant, with estimated anagenetic rates of 0). Inferences with DEC+J can in some cases depart dramatically from intuition, e.g. when highly unparsimonious numbers of jump dispersal events are required solely because j is maximized. Statistical comparison with DEC is inappropriate because a higher DEC+J likelihood does not reflect a more close approximation of the “true” model of range evolution, which surely must include time-dependent processes; instead, it is simply due to more weight being allocated (via j) to jump dispersal events whose time-dependent probabilities are ignored. In testing hypotheses about the geographic mode of speciation, jump dispersal can and should instead be modelled using existing frameworks for state-dependent lineage diversification in continuous time, taking appropriate cautions against Type I errors associated with such methods. For simple inference of ancestral ranges on a fixed phylogeny, a DEC-based model may be defensible if statistical model selection is not used to justify the choice, and it is understood that inferences about cladogenetic range inheritance lack any relation to time, normally a fundamental axis of evolutionary models.

Plant functional trait change across a warming tundra biome

Abstract: The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature-trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

Abstract: Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases.

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

Abstract: The idea that noncrop habitat enhances pest control and represents a win-win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win-win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies.

The clustering of the SDSS-IV extended Baryon Oscillation Spectroscopic Survey DR14 quasar sample: first measurement of Baryon Acoustic Oscillations between redshift 0.8 and 2.2

Abstract: We present measurements of the Baryon Acoustic Oscillation (BAO) scale in redshift-space using the clustering of quasars. We consider a sample of 147 000 quasars from the extended Baryon Oscillation Spectroscopic Survey (eBOSS) distributed over 2044 square degrees with redshifts 0.8 0 at 6.6s significance when testing a ΛCDM model with free curvature.