The N-methyl-d-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat

Long-term morphological synaptic changes associated with homosynaptic long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) in vivo, in awake adult rats were analyzed using three-dimensional (3-D) reconstructions of electron microscope images of ultrathin serial sections from the molecular layer of the dentate gyrus. For the first time in morphological studies, the specificity of the effects of LTP and LTD on both spine and synapse ultrastructure was determined using an N-methyl-d-aspartate (NMDA) receptor antagonist CPP (3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid). There were no differences in synaptic density 24 h after LTP or LTD induction, and CPP alone had no effect on synaptic density. LTP increased significantly the proportion of mushroom spines, whereas LTD increased the proportion of thin spines, and both LTP and LTD decreased stubby spine number. Both LTP and LTD increased significantly spine head evaginations (spinules) into synaptic boutons and CPP blocked these changes. Synaptic boutons were smaller after LTD, indicating a pre-synaptic effect. Interestingly, CPP alone decreased bouton and mushroom spine volumes, as well as post-synaptic density (PSD) volume of mushroom spines.These data show similarities, but also some clear differences, between the effects of LTP and LTD on spine and synaptic morphology. Although CPP blocks both LTP and LTD, and impairs most morphological changes in spines and synapses, CPP alone was shown to exert effects on aspects of spine and synaptic structure

Constraining Sources of Ultra High Energy Cosmic Rays Using High Energy Observations with the Fermi Satellite

We analyze the conditions that enable acceleration of particles to ultra-high energies, ~10^{20} eV (UHECRs). We show that broad band photon data recently provided by WMAP, ISOCAM, Swift and Fermi satellites, yield constraints on the ability of active galactic nuclei (AGN) to produce UHECRs. The high energy (MeV - GeV) photons are produced by Compton scattering of the emitted low energy photons and the cosmic microwave background or extra-galactic background light. The ratio of the luminosities at high and low photon energies can therefore be used as a probe of the physical conditions in the acceleration site. We find that existing data excludes core regions of nearby radio-loud AGN as possible acceleration sites of UHECR protons. However, we show that giant radio lobes are not excluded. We apply our method to Cen A, and show that acceleration of protons to ~10^{20} eV can only occur at distances >~ 100 kpc from the core.Comment: Extended discussion on former results; Accepted for publication in JCA

An Analytical Study on the Multi-critical Behaviour and Related Bifurcation Phenomena for Relativistic Black Hole Accretion

We apply the theory of algebraic polynomials to analytically study the transonic properties of general relativistic hydrodynamic axisymmetric accretion onto non-rotating astrophysical black holes. For such accretion phenomena, the conserved specific energy of the flow, which turns out to be one of the two first integrals of motion in the system studied, can be expressed as a 8$^{th}$ degree polynomial of the critical point of the flow configuration. We then construct the corresponding Sturm's chain algorithm to calculate the number of real roots lying within the astrophysically relevant domain of $\mathbb{R}$. This allows, for the first time in literature, to {\it analytically} find out the maximum number of physically acceptable solution an accretion flow with certain geometric configuration, space-time metric, and equation of state can have, and thus to investigate its multi-critical properties {\it completely analytically}, for accretion flow in which the location of the critical points can not be computed without taking recourse to the numerical scheme. This work can further be generalized to analytically calculate the maximal number of equilibrium points certain autonomous dynamical system can have in general. We also demonstrate how the transition from a mono-critical to multi-critical (or vice versa) flow configuration can be realized through the saddle-centre bifurcation phenomena using certain techniques of the catastrophe theory.Comment: 19 pages, 2 eps figures, to appear in "General Relativity and Gravitation

eIF2B bodies and their role in the integrated stress response

Eukaryotic initiation factor 2 (eIF2) is a G protein comprised of 3 subunits (α, β and γ) that is critical for translation. It is tightly regulated in the integrated stress response (ISR) via the phosphorylation of its α subunit following the induction of cellular stress. In its phosphorylated form eIF2α inhibits the guanine nucleotide exchange factor (GEF) eukaryotic initiation factor 2B (eIF2B), resulting in the attenuation of global protein synthesis. eIF2B is a multisubunit protein comprised of regulatory and catalytic subunits. The catalytic subunits are responsible for the GEF activity whereas the regulatory subunits mediate inhibition by phosphorylated eIF2α. Through studying the localisation of eIF2B subunits, cytoplasmic eIF2B bodies were identified in mammalian cells. A relationship between body size and the eIF2B subunits localising to them exists; larger bodies contain all subunits and smaller bodies contain predominantly catalytic subunits. eIF2 localises to eIF2B bodies and moves through these bodies in a manner that correlates with eIF2B GEF activity. Upon the induction of cellular stress phosphorylated eIF2α localises predominately to larger eIF2B bodies which contain regulatory subunits and a decrease in the movement of eIF2 through these bodies is observed. Interestingly, drugs that inhibit the ISR can rescue the movement of eIF2 through these eIF2B bodies, in a manner that correlates to cellular levels of phosphorylated eIF2α. In contrast, smaller eIF2B bodies, which contain predominately catalytic subunits, show increased movement of eIF2 during cellular stress. This increase in movement is accompanied by an increase in the localisation of eIF2Bδ to these bodies, suggesting the formation of a novel eIF2B subcomplex. This response is mimicked by ISR-inhibiting drugs, providing insight into their potential mechanisms of action. This study provides the first evidence that the composition and function of mammalian eIF2B bodies is regulated by the ISR and the drugs that control it

Search for long-lived neutral particles in pp collisions at s√=13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

This paper describes a search for pairs of neutral, long-lived particles decaying in the ATLAS calorimeter. Long-lived particles occur in many extensions to the Standard Model and may elude searches for new promptly decaying particles. The analysis considers neutral, long-lived scalars with masses between 5 and 400 GeV, produced from decays of heavy bosons with masses between 125 and 1000 GeV, where the long-lived scalars decay into Standard Model fermions. The analysis uses either 10.8 fb−1 or 33.0 fb−1 of data (depending on the trigger) recorded in 2016 at the LHC with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of 13 TeV. No significant excess is observed, and limits are reported on the production cross section times branching ratio as a function of the proper decay length of the long-lived particles

Effect of Price Variation on Rice Production in Nigeria (1970-2011)

Food price instability is a frequent forerunner of macroeconomic shocks and political turmoil that can discourage long-run investment and curtail growth. There is a general shortage in the domestic supply of food grains in Nigeria; this has often resulted in increased market prices of the commodities, thus leading to change in the prices of rice overtime.The main thrust of this study is to unveil the effect of price variation on production of rice in Nigeria. This study employed time series data of a period of 42years. The following recommendations were made: The government should stabilize the quantity of rice produced in the country; more effort should be given to production of rice considering its relevance to food security. The Cobweb theory can Be used by the government to regulate the response of price to rice production

Genetic polymorphisms of innate and adaptive immunity as predictors of outcome in critically ill patients

Sepsis and septic shock frequently cause the admission or complicate the clinical course of critically ill patients admitted in the intensive care units (ICU). Genetic variations disrupting the immune sensing of infectious organisms, could affect the ability of the immune system to respond to infection, and may influence both the genetic predisposition to infection and the diversity of the clinical presentation of sepsis. The aim of this study was to uncover possible associations between common functional immune gene polymorphisms (of both innate and adaptive immunity) and ICU-acquired sepsis and mortality. The TLR4-D299G (rs4986790), TLR4-T3991 (rs4986791), C2-c.841_849+19del28 (rs9332736), TACI-C104R (rs34557412), BAFFR-P21R (rs77874543), and BAFFR-H159Y (rs61756766) polymorphisms were detected in a cohort of 215 critically ill patients, admitted in an 8-bed medical/surgical ICU. Interestingly, TLR4-D299G, TLR4-T3991 and BAFFR-P21R carriage was associated with a lower risk of ICU-acquired sepsis. This association applied particularly in medical patients, while in trauma and surgical patients no significant associations were observed. Moreover, carriers of TACI-C104R displayed an undiagnosed mild to moderate hypogammaglobulinemia along with a significantly lower survival rate in the ICU, although lethal events were not attributed to sepsis. These findings further elucidate the role that host immune genetic variations may play in the susceptibility to ICU-acquired sepsis and ICU mortality. (C) 2014 Elsevier GmbH. All rights reserved