Global biome patterns of the Middle and Late Pleistocene

Our primary aim was to assess the hypothesis that distinctive features of the patterns of vegetation change during successive Quaternary glacial–interglacial cycles reflect climatic differences arising from forcing differences. We addressed this hypothesis using 207 half-degree resolution global biome pattern simulations, for time slices between 800 and 2 ka, made using the LPJ-GUESS dynamic global vegetation model. Simulations were driven using ice-core atmospheric CO2 concentrations, Earth's obliquity, and outputs from a pre-industrial and 206 palaeoclimate experiments; four additional simulations were driven using projected future CO2 concentrations. Climate experiments were run using HadCM3. Using a rule-based approach, above-ground biomass and leaf area index of LPJ-GUESS plant functional types were used to infer each grid cell's biome. The hypothesis is supported by the palaeobiome simulations. To enable comparisons with the climatic forcing, multivariate analyses were performed of global vegetation pattern dissimilarities between simulations. Results showed generally similar responses to glacial–interglacial climatic variations during each cycle, although no two interglacials or glacials had identical biome patterns. Atmospheric CO2 concentration was the strongest driver of the dissimilarity patterns. Dissimilarities relative to the time slice with the lowest atmospheric CO2 concentration show the log-linear relationship to atmospheric CO2 concentration expected of an index of ecocarbon sensitivity. For each simulation, extent and total above-ground biomass of each biome were calculated globally and for three longitudinal segments corresponding to the major continental regions. Mean and minimum past extents of forest biomes, notably Temperate Summergreen Forest, in the three major continental regions strongly parallel relative tree diversities, hence supporting the hypothesis that past biome extents played an important role in determining present diversity. Albeit that they reflect the climatic consequences only of the faster Earth system components, simulated potential future biome patterns are unlike any during the past 800 ky, and likely will continue to change markedly for millennia if projected CO2 concentrations are realised

Brain perfusion patterns are altered in chronic knee pain:a spatial covariance analysis of arterial spin labelling MRI

Chronic musculoskeletal pain is a common problem globally. Current evidence suggests that maladapted central pain pathways are associated with pain chronicity, for example, in postoperative pain after knee replacement. Other factors such as low mood, anxiety, and tendency to catastrophize are also important contributors. We aimed to investigate brain imaging features that underpin pain chronicity based on multivariate pattern analysis of cerebral blood flow (CBF), as a marker of maladaptive brain changes. This was achieved by identifying CBF patterns that discriminate chronic pain from pain-free conditions and by exploring their explanatory power for factors thought to drive pain chronification. In 44 chronic knee pain and 29 pain-free participants, we acquired both CBF and T1-weighted data. Participants completed questionnaires related to affective processes and pressure and cuff algometry to assess pain sensitization. Two factor scores were extracted from these scores representing negative affect and pain sensitization. A spatial covariance principal component analysis of CBF identified 5 components that significantly discriminated chronic pain participants from controls, with the unified network achieving 0.83 discriminatory accuracy (area under the curve). In chronic knee pain, significant patterns of relative hypoperfusion were evident in anterior default-mode and salience network hubs, while hyperperfusion was seen in posterior default mode, thalamus, and sensory regions. One component correlated positively with the pain sensitization score (r = 0.43, P = 0.006), suggesting that this CBF pattern reflects neural activity changes encoding pain sensitization. Here, we report a distinct chronic knee pain-related representation of CBF, pointing toward a brain signature underpinning central aspects of pain sensitization

Novel role of PKR in inflammasome activation and HMGB1 release

The inflammasome regulates release of caspase activation-dependent cytokines, including IL-1β, IL-18, and high-mobility group box 1 (HMGB1)1-5. During the course of studying HMGB1 release mechanisms, we discovered an important role of double-stranded RNA dependent protein kinase (PKR) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminum, rotenone, live E. coli, anthrax lethal toxin, DNA transfection, and S. Typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1beta, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with multiple inflammasome components, including NLR family pyrin domain-containing 3 (NLRP3), NLR family pyrin domain-containing 1 (NLRP1), NLR family CARD domain-containing protein 4 (NLRC4), Absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell free system with recombinant NLRP3, ASC and pro-casapse-1 reconstitutes inflammasome activity. These results reveal a critical role of PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation

SPIDER VII - Revealing the Stellar Population Content of Massive Early-type Galaxies out to 8Re

Radial trends of stellar populations in galaxies provide a valuable tool to understand the mechanisms of galaxy growth. In this paper, we present the first comprehensive analysis of optical-optical and optical-NIR colours, as a function of galaxy mass, out to the halo region (8Re) of early-type galaxies (ETGs). We select a sample of 674 massive ETGs (M*>3x10^10MSun) from the SDSS-based SPIDER survey. By comparing with a large range of population synthesis models, we derive robust constraints on the radial trends in age and metallicity. Metallicity is unambiguously found to decrease outwards, with a measurable steepening of the slope in the outer regions (Re<R<8Re). The gradients in stellar age are found to be more sensitive to the models used, but in general, the outer regions of ETGs feature older populations compared to the cores. This trend is strongest for the most massive galaxies in our sample (M*>10^11MSun). Furthermore, when segregating with respect to large scale environment, the age gradient is more significant in ETGs residing in higher density regions. These results shed light on the processes leading from the formation of the central core to the growth of the stellar envelope of massive galaxies. The fact that the populations in the outer regions are older and more metal-poor than in the core suggests a process whereby the envelope of massive galaxies is made up of accreted small satellites (i.e. minor mergers) whose stars were born during the first stages of galaxy formation.Comment: 20 pages, 13 figures, 10 tables. Accepted for publication in MNRA

A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways

Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated by intricate and multimodal QS signal transduction processes. The LuxS/AI-2 QS system is highly conserved among Eubacteria and AI-2 is reported as a ‘universal' signal molecule. To understand the hierarchical organization of AI-2 circuitry, a comprehensive approach incorporating stochastic simulations was developed. We investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several discoveries: (1) the mRNA transcript and protein levels of AI-2 synthases, Pfs and LuxS, do not contribute to the dramatically increased level of AI-2 found when cells are grown in the presence of glucose; (2) a concomitant increase in metabolic flux through this synthesis pathway in the presence of glucose only partially accounts for this difference. We predict that ‘high-flux' alternative pathways or additional biological steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work demonstrates the utility of linking cell physiology with systems-based stochastic models that can be assembled de novo with partial knowledge of biochemical pathways

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc