Improvements in the fossil record may largely resolve current conflicts between morphological and molecular estimates of mammal phylogeny

Phylogenies of mammals based on morphological data continue to show several major areas of conflict with the current consensus view of their relationships, which is based largely on molecular data. This raises doubts as to whether current morphological character sets are able to accurately resolve mammal relationships. We tested this under a hypothetical ‘best case scenario’ by using ancestral state reconstruction (under both maximum parsimony and maximum likelihood) to infer the morphologies of fossil ancestors for all clades present in a recent comprehensive DNA sequencebased phylogeny of mammals, and then seeing what effect the subsequent inclusion of these predicted ancestors had on unconstrained phylogenetic analyses of morphological data. We found that this resulted in topologies that are highly congruent with the current consensus phylogeny, at least when the predicted ancestors are assumed to be well preserved and densely sampled. Most strikingly, several analyses recovered the monophyly of clades that have never been found in previous morphology-only studies, such as Afrotheria and Laurasiatheria. Our results suggest that, at least in principle, improvements in the fossil record—specifically the discovery of fossil taxa that preserve the ancestral or near-ancestral morphologies of the nodes in the current consensus—may be sufficient to largely reconcile morphological and molecular estimates of mammal phylogeny, even using current morphological character set

Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma

Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survival and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM – a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM. In this study, we describe a mechanism by which increased expression of peptidyl arginine deiminase 2 (PADI2) by BMMSCs in patients with MGUS and MM directly alters malignant plasma cell phenotype. We identify PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through its enzymatic deimination of histone H3 arginine 26, PADI2 activity directly induces the upregulation of interleukin-6 (IL-6) expression. This leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Activation of Estrogen Receptor-α by E2 or EGF Induces Temporally Distinct Patterns of Large-Scale Chromatin Modification and mRNA Transcription

Estrogen receptor-α (ER) transcription function is regulated in a ligand-dependent (e.g., estradiol, E2) or ligand-independent (e.g., growth factors) manner. Our laboratory seeks to understand these two modes of action. Using a cell line that contains a visible prolactin enhancer/promoter array (PRL-HeLa) regulated by ER, we analyzed ER response to E2 and EGF by quantifying image-based results. Data show differential recruitment of GFP-ER to the array, with the AF1 domain playing a vital role in EGF-mediated responsiveness. Temporal analyses of large-scale chromatin dynamics, and accumulation of array-localized reporter mRNA over 24 hours showed that the EGF response consists of a single pulse of reporter mRNA accumulation concomitant with transient increase in array decondensation. Estradiol induced a novel cyclical pattern of mRNA accumulation with a sustained increase in array decondensation. Collectively, our work shows that there is a stimuli-specific pattern of large-scale chromatin modification and transcript levels by ER

The effect of cataract on early stage glaucoma detection using spatial and temporal contrast sensitivity tests

Background: To investigate the effect of cataract on the ability of spatial and temporal contrast sensitivity tests used to detect early glaucoma. Methods: Twenty-seven glaucoma subjects with early cataract (mean age 60 ±10.2 years) which constituted the test group were recruited together with twenty-seven controls (cataract only) matched for age and cataract type from a primary eye care setting. Contrast sensitivity to flickering gratings at 20 Hz and stationary gratings with and without glare, were measured for 0.5, 1.5 and 3 cycles per degree (cpd) in central vision. Perimetry and structural measurements with the Heidelberg Retinal Tomograph (HRT) were also performed. Results: After considering the effect of cataract, contrast sensitivity to stationary gratings was reduced in the test group compared with controls with a statistically significant mean difference of 0.2 log units independent of spatial frequency. The flicker test showed a significant difference between test and control group at 1.5 and 3 cpd (p = 0.019 and p = 0.011 respectively). The percentage of glaucoma patients who could not see the temporal modulation was much higher compared with their cataract only counterparts. A significant correlation was found between the reduction of contrast sensitivity caused by glare and the Glaucoma Probability Score (GPS) as measured with the HRT (p<0.005). Conclusions: These findings indicate that both spatial and temporal contrast sensitivity tests are suitable for distinguishing between vision loss as a consequence of glaucoma and vision loss caused by cataract only. The correlation between glare factor and GPS suggests that there may be an increase in intraocular stray light in glaucoma

Primary Black Hole Spin in OJ 287 as Determined by the General Relativity Centenary Flare

OJ 287 is a quasi-periodic quasar with roughly 12 year optical cycles. It displays prominent outbursts that are predictable in a binary black hole model. The model predicted a major optical outburst in 2015 December. We found that the outburst did occur within the expected time range, peaking on 2015 December 5 at magnitude 12.9 in the optical R -band. Based on Swift /XRT satellite measurements and optical polarization data, we find that it included a major thermal component. Its timing provides an accurate estimate for the spin of the primary black hole, ##IMG## [http://ej.iop.org/images/2041-8205/819/2/L37/apjl523055ieqn1.gif] $i =0.313pm 0.01$ . The present outburst also confirms the established general relativistic properties of the system such as the loss of orbital energy to gravitational radiation at the 2% accuracy level, and it opens up the possibility of testing the black hole no-hair theorem with 10% accuracy during the present decade.Peer reviewe

Mechanical and Assembly Units of Viral Capsids Identified via Quasi-Rigid Domain Decomposition

Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV) for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available