UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

Who should be prioritized for renal transplantation?: Analysis of key stakeholder preferences using discrete choice experiments

Background Policies for allocating deceased donor kidneys have recently shifted from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK and USA. Newer allocation algorithms incorporate waiting time as a primary factor, and in the UK, young adults are also favoured. However, there is little contemporary UK research on the views of stakeholders in the transplant process to inform future allocation policy. This research project aimed to address this issue. Methods Discrete Choice Experiment (DCE) questionnaires were used to establish priorities for kidney transplantation among different stakeholder groups in the UK. Questionnaires were targeted at patients, carers, donors / relatives of deceased donors, and healthcare professionals. Attributes considered included: waiting time; donor-recipient HLA match; whether a recipient had dependents; diseases affecting life expectancy; and diseases affecting quality of life. Results Responses were obtained from 908 patients (including 98 ethnic minorities); 41 carers; 48 donors / relatives of deceased donors; and 113 healthcare professionals. The patient group demonstrated statistically different preferences for every attribute (i.e. significantly different from zero) so implying that changes in given attributes affected preferences, except when prioritizing those with no rather than moderate diseases affecting quality of life. The attributes valued highly related to waiting time, tissue match, prioritizing those with dependents, and prioritizing those with moderate rather than severe diseases affecting life expectancy. Some preferences differed between healthcare professionals and patients, and ethnic minority and non-ethnic minority patients. Only non-ethnic minority patients and healthcare professionals clearly prioritized those with better tissue matches. Conclusions Our econometric results are broadly supportive of the 2006 shift in UK transplant policy which emphasized prioritizing the young and long waiters. However, our findings suggest the need for a further review in the light of observed differences in preferences amongst ethnic minorities, and also because those with dependents may be a further priority.</p

Cross-talk between cd1d-restricted nkt cells and γδ cells in t regulatory cell response

CD1d is a non-classical major histocompatibility class 1-like molecule which primarily presents either microbial or endogenous glycolipid antigens to T cells involved in innate immunity. Natural killer T (NKT) cells and a subpopulation of γδ T cells expressing the Vγ4 T cell receptor (TCR) recognize CD1d. NKT and Vγ4 T cells function in the innate immune response via rapid activation subsequent to infection and secrete large quantities of cytokines that both help control infection and modulate the developing adaptive immune response. T regulatory cells represent one cell population impacted by both NKT and Vγ4 T cells. This review discusses the evidence that NKT cells promote T regulatory cell activation both through direct interaction of NKT cell and dendritic cells and through NKT cell secretion of large amounts of TGFβ, IL-10 and IL-2. Recent studies have shown that CD1d-restricted Vγ4 T cells, in contrast to NKT cells, selectively kill T regulatory cells through a caspase-dependent mechanism. Vγ4 T cell elimination of the T regulatory cell population allows activation of autoimmune CD8+ effector cells leading to severe cardiac injury in a coxsackievirus B3 (CVB3) myocarditis model in mice. CD1d-restricted immunity can therefore lead to either immunosuppression or autoimmunity depending upon the type of innate effector dominating during the infection

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

Reconciled climate response estimates from climate models and the energy budget of Earth

Climate risks increase with mean global temperature, so knowledge about the amount of future global warming should better inform risk assessments for policymakers. Expected near-term warming is encapsulated by the transient climate response (TCR), formally defined as the warming following 70 years of 1% per year increases in atmospheric CO2 concentration, by which point atmospheric CO2 has doubled. Studies based on Earth’s historical energy budget have typically estimated lower values of TCR than climate models, suggesting that some models could overestimate future warming. However, energy-budget estimates rely on historical temperature records that are geographically incomplete and blend air temperatures over land and sea ice with water temperatures over open oceans. We show that there is no evidence that climate models overestimate TCR when their output is processed in the same way as the HadCRUT4 observation-based temperature record3, 4. Models suggest that air-temperature warming is 24% greater than observed by HadCRUT4 over 1861–2009 because slower-warming regions are preferentially sampled and water warms less than air5. Correcting for these biases and accounting for wider uncertainties in radiative forcing based on recent evidence, we infer an observation-based best estimate for TCR of 1.66 °C, with a 5–95% range of 1.0–3.3 °C, consistent with the climate models considered in the IPCC 5th Assessment Report

The Cow: Discovery of a Luminous, Hot, and Rapidly Evolving Transient

We present the ATLAS discovery and initial analysis of the first 18 days of the unusual transient event, ATLAS18qqn/AT2018cow. It is characterized by a high peak luminosity (~1.7 × 1044 erg s−1), rapidly evolving light curves (>5 mag rise to peak in ~3.5 days), and hot blackbody spectra, peaking at ~27,000 K that are relatively featureless and unchanging over the first two weeks. The bolometric light curve cannot be powered by radioactive decay under realistic assumptions. The detection of high-energy emission may suggest a central engine as the powering source. Using a magnetar model, we estimated an ejected mass of 0.1–0.4 M ${}_{\odot }$, which lies between that of low-energy core-collapse events and the kilonova, AT2017gfo. The spectra cooled rapidly from 27,000 to 15,000 K in just over two weeks but remained smooth and featureless. Broad and shallow emission lines appear after about 20 days, and we tentatively identify them as He i although they would be redshifted from their rest wavelengths. We rule out that there are any features in the spectra due to intermediate mass elements up to and including the Fe group. The presence of r-process elements cannot be ruled out. If these lines are due to He, then we suggest a low-mass star with residual He as a potential progenitor. Alternatively, models of magnetars formed in neutron star mergers, or accretion onto a central compact object, give plausible matches to the data

Observations of the GRB Afterglow ATLAS17aeu and Its Possible Association with GW170104

We report the discovery and multiwavelength data analysis of the peculiar optical transient, ATLAS17aeu. This transient was identified in the sky map of the LIGO gravitational wave event GW 170104 by our ATLAS and Pan-STARRS coverage. ATLAS17aeu was discovered 23.1 hr after GW 170104 and rapidly faded over the next three nights, with a spectrum revealing a blue featureless continuum. The transient was also detected as a fading X-ray source by Swift and in the radio at 6 and 15 GHz. The gamma-ray burst GRB 170105A was detected by three satellites 19.04 hr after GW 170104 and 4.10 hr before our first optical detection. We analyze the multiwavelength fluxes in the context of the known GRB population and discuss the observed sky rates of GRBs and their afterglows. We find it statistically likely that ATLAS17aeu is an afterglow associated with GRB 170105A, with a chance coincidence ruled out at the 99% confidence or 2.6 sigma. A long, soft GRB within a redshift range of 1 less than or similar to z less than or similar to 2.9 would be consistent with all the observed multiwavelength data. The Poisson probability of a chance occurrence of GW 170104 and ATLAS17aeu is p = 0.04. This is the probability of a chance coincidence in 2D sky location and in time. These observations indicate that ATLAS17aeu is plausibly a normal GRB afterglow at significantly higher redshift than the distance constraint for GW 170104 and therefore a chance coincidence. However, if a redshift of the faint host were to place it within the GW 170104 distance range, then physical association with GW 170104 should be considered

Dietary Restriction Depends on Nutrient Composition to Extend Chronological Lifespan in Budding Yeast Saccharomyces cerevisiae

10.1371/journal.pone.0064448PLoS ONE85

The Rossiter-McLaughlin effect in Exoplanet Research

The Rossiter-McLaughlin effect occurs during a planet's transit. It provides the main means of measuring the sky-projected spin-orbit angle between a planet's orbital plane, and its host star's equatorial plane. Observing the Rossiter-McLaughlin effect is now a near routine procedure. It is an important element in the orbital characterisation of transiting exoplanets. Measurements of the spin-orbit angle have revealed a surprising diversity, far from the placid, Kantian and Laplacian ideals, whereby planets form, and remain, on orbital planes coincident with their star's equator. This chapter will review a short history of the Rossiter-McLaughlin effect, how it is modelled, and will summarise the current state of the field before describing other uses for a spectroscopic transit, and alternative methods of measuring the spin-orbit angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Centre–surround inhibition is a general aspect of famous-person recognition: evidence from negative semantic priming from clearly visible primes

A Centre-Surround Attentional Mechanism was proposed by Carr and Dagenbach (1990) to account for their observations of negative semantic priming from hard-to-perceive primes. The mechanism cannot account for the observation of negative semantic priming when primes are clearly visible. Three experiments (n = 30, 46, and 30) used a familiarity decision to names of famous people preceded by prime names of the same or different occupation. Negative semantic priming was observed at 150 or 200ms SOA with positive priming at shorter (50ms) and longer (1000ms) SOA. Experiment 3 verified that the primes were easily recognisable in the priming task at a SOA that yielded negative semantic priming, which cannot be predicted by the original Centre-Surround mechanism. A modified version is proposed that explains transiently negative semantic priming by proposing that Centre-Surround inhibition is a normal, automatically invoked aspect of the semantic processing of visually-presented famous names