2,551 research outputs found
Molecular Basis for poly(A) RNP Architecture and Recognition by the Pan2-Pan3 Deadenylase
The stability of eukaryotic mRNAs is dependent on a ribonucleoprotein (RNP) complex of poly(A)-binding proteins (PABPC1/Pab1) organized on the poly(A) tail. This poly(A) RNP not only protects mRNAs from premature degradation but also stimulates the Pan2-Pan3 deadenylase complex to catalyze the first step of poly(A) tail shortening. We reconstituted this process in vitro using recombinant proteins and show that Pan2-Pan3 associates with and degrades poly(A) RNPs containing two or more Pab1 molecules. The cryo-EM structure of Pan2-Pan3 in complex with a poly(A) RNP composed of 90 adenosines and three Pab1 protomers shows how the oligomerization interfaces of Pab1 are recognized by conserved features of the deadenylase and thread the poly(A) RNA substrate into the nuclease active site. The structure reveals the basis for the periodic repeating architecture at the 3' end of cytoplasmic mRNAs. This illustrates mechanistically how RNA-bound Pab1 oligomers act as rulers for poly(A) tail length over the mRNAs' lifetime.We would like to thank ... the MPIB cryo-EM, and core facilities ..
Cryo-Preparation and Planar Magnetron Sputtering for Low Temperature Scanning Electron Microscopy
Cryo-preparation is a reliable technique for the structural investigation of food products in low temperature scanning electron microscopy (SEM). Artifacts, such as, the segregation of water/non-water ingredients, occur during the freezing process by the crystallization of ice; they can be helpful for correct interpretation of visualized details, e.g., the detection of water containing compartments. The size of the segregation structures depends on water concentration and specimen thickness. The condensation of water vapor (ice contamination) is influenced by the specimen temperature and the partial pressure of the water inside the vacuum system. Furthermore, the evaporation (sublimation, etching) of specimen water can be regulated by monitoring the specimen temperature. Sublimation under SEM observation, i.e., in situ etching at low acceleration voltage, allows the progress of etching to be observed continuously, prior to the coating of the specimen inside a dedicated cryo-preparation system attached to the SEM. Coating of specimens provides superior structural resolution compared with the observation of uncoated samples. A coating layer of platinum ( ~ 1-2 nm thick), deposited on a cold substrate by planar magnetron sputtering, is almost homogenous and has a density close to that of the solid metal. Its use allows bulk biological specimens to be observed in low temperature SEM with a structural resolution up to the visualization of transmembrane proteins
Transcriptomic effects of adenosine 2A receptor deletion in healthy and endotoxemic murine myocardium
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, \u3c5 \u3e% FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2. Few canonical paths were impacted, with altered Gnb1, Prkar2b, Pde3b and Map3k2 (among others) implicating modified G protein/cAMP/PKA and cGMP/NOS signalling. Lipopolysaccharide (LPS; 20 mg/kg) challenge for 24 h modified \u3e4100 transcripts in wild-type (WT) myocardium (≥1.5-fold change, FDR \u3c 1 %); the most induced are Lcn2 (+590); Saa3 (+516); Serpina3n (+122); Cxcl9 (+101) and Cxcl1 (+89) and the most repressed are Car3 (−38); Adipoq (−17); Atgrl1/Aplnr (−14); H19 (−11) and Itga8 (−8). Canonical responses centred on inflammation, immunity, cell death and remodelling, with pronounced amplification of toll-like receptor (TLR) and underlying JAK-STAT, NFκB and MAPK pathways, and a ‘cardio-depressant’ profile encompassing suppressed ß-adrenergic, PKA and Ca2+ signalling, electromechanical and mitochondrial function (and major shifts in transcripts impacting function/injury including Lcn2, S100a8/S100a9, Icam1/Vcam and Nox2 induction, and Adipoq, Igf1 and Aplnr repression). Endotoxemic responses were selectively modified by A2AR KO, supporting inflammatory suppression via A2AR sensitive shifts in regulators of NFκB and JAK-STAT signalling (IκBζ, IκBα, STAT1, CDKN1a and RRAS2) without impacting the cardio-depressant gene profile. Data indicate A2ARs exert minor effects in un-stressed myocardium and selectively suppress NFκB and JAK-STAT signalling and cardiac injury without influencing cardiac depression in endotoxemia
Petrologic and Geochemical Composition of the AND-2A Core, ANDRILL Southern McMurdo Sound Project, Antartica
The compositional record of the AND-2A drillcore is examined using petrological, sedimentological, volcanological and geochemical analysis of clasts, sediments and pore waters. Preliminary investigations of basement clasts (granitoids and metasediments) indicate both local and distal sources corresponding to variable ice-volume and ice-flow directions. Low abundance of sedimentary clasts (e.g., arkose, litharenite) suggests reduced contributions from sedimentary covers while intraclasts (e.g., diamictite, conglomerate) attest to intrabasinal reworking. Volcanic material includes pyroclasts (e.g., pumice, scoria), sediments and lava. Primary and reworked tephra layers occur within the Early Miocene interval (1093 to 640 metres below sea floor). The compositions of volcanic clasts reveal a diversity of alkaline types derived from the McMurdo Volcanic Group. Finer-grained sediments (e.g., sandstone, siltstone) show increases in biogenic silica and volcanic glass from 230 to 780 mbsf and higher proportions of terrigenous material ca. 350 to 750 mbsf and below 970 mbsf. Basement clast assemblages suggest a dominant provenance from the Skelton Glacier - Darwin Glacier area and from the Ferrar Glacier - Koettlitz Glacier area. Provenance of sand grains is consistent with clast sources. Thirteen Geochemical Units are established based on compositional trends derived from continuous XRF scanning. High values of Fe and Ti indicate terrigenous and volcanic sources, whereas high Ca values signify either biogenic or diagenic sources. Highly alkaline and saline pore waters were produced by chemical exchange with glass at moderately elevated temperatures
Over-the-scope clip (OTSC (R)) closure of a recto-acetabular fistula
A 25-year-old male Syrian refugee presented in our hospital with recurrent hip infections after having undergone hip arthroplasty abroad following destruction of his right hip joint by shell splinters in the Syrian civil war. The patient underwent hip arthroplasty revision with implantation of a cement spacer. CT-scan with rectal contrast media filling revealed a rectoacetabular fistula. Consecutively, the patient underwent ileostomy formation. The fistula was then successfully closed by endoscopic over-the-scope clipping (OTSC (R)). Fistulas between intestines and joints rarely develop and in the few cases published mostly extensive abdominal rescue surgery has been performed. Here, we present a case of a traumatic rectoacetabular fistula that was successfully closed by OTSC. This innovative method could represent a safe and suitable option to effectively close fistulas between joints and intestines thereby avoiding extensive rescue surgery with bowel resection or permanent ostomy
Charge separation relative to the reaction plane in Pb-Pb collisions at TeV
Measurements of charge dependent azimuthal correlations with the ALICE
detector at the LHC are reported for Pb-Pb collisions at TeV. Two- and three-particle charge-dependent azimuthal correlations in
the pseudo-rapidity range are presented as a function of the
collision centrality, particle separation in pseudo-rapidity, and transverse
momentum. A clear signal compatible with a charge-dependent separation relative
to the reaction plane is observed, which shows little or no collision energy
dependence when compared to measurements at RHIC energies. This provides a new
insight for understanding the nature of the charge dependent azimuthal
correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286
Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider
Measurements of multi-particle azimuthal correlations (cumulants) for charged
particles in p-Pb and Pb-Pb collisions are presented. They help address the
question of whether there is evidence for global, flow-like, azimuthal
correlations in the p-Pb system. Comparisons are made to measurements from the
larger Pb-Pb system, where such evidence is established. In particular, the
second harmonic two-particle cumulants are found to decrease with multiplicity,
characteristic of a dominance of few-particle correlations in p-Pb collisions.
However, when a gap is placed to suppress such correlations,
the two-particle cumulants begin to rise at high-multiplicity, indicating the
presence of global azimuthal correlations. The Pb-Pb values are higher than the
p-Pb values at similar multiplicities. In both systems, the second harmonic
four-particle cumulants exhibit a transition from positive to negative values
when the multiplicity increases. The negative values allow for a measurement of
to be made, which is found to be higher in Pb-Pb collisions at
similar multiplicities. The second harmonic six-particle cumulants are also
found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find
which is indicative of a Bessel-Gaussian
function for the distribution. For very high-multiplicity Pb-Pb
collisions, we observe that the four- and six-particle cumulants become
consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and
Pb-Pb are measured. These are found to be similar for overlapping
multiplicities, when a gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87
Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR
Substantial experimental and theoretical efforts worldwide are devoted to
explore the phase diagram of strongly interacting matter. At LHC and top RHIC
energies, QCD matter is studied at very high temperatures and nearly vanishing
net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was
created at experiments at RHIC and LHC. The transition from the QGP back to the
hadron gas is found to be a smooth cross over. For larger net-baryon densities
and lower temperatures, it is expected that the QCD phase diagram exhibits a
rich structure, such as a first-order phase transition between hadronic and
partonic matter which terminates in a critical point, or exotic phases like
quarkyonic matter. The discovery of these landmarks would be a breakthrough in
our understanding of the strong interaction and is therefore in the focus of
various high-energy heavy-ion research programs. The Compressed Baryonic Matter
(CBM) experiment at FAIR will play a unique role in the exploration of the QCD
phase diagram in the region of high net-baryon densities, because it is
designed to run at unprecedented interaction rates. High-rate operation is the
key prerequisite for high-precision measurements of multi-differential
observables and of rare diagnostic probes which are sensitive to the dense
phase of the nuclear fireball. The goal of the CBM experiment at SIS100
(sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD
matter: the phase structure at large baryon-chemical potentials (mu_B > 500
MeV), effects of chiral symmetry, and the equation-of-state at high density as
it is expected to occur in the core of neutron stars. In this article, we
review the motivation for and the physics programme of CBM, including
activities before the start of data taking in 2022, in the context of the
worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal
Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at = 5.02 TeV
Two-particle angular correlations between unidentified charged trigger and
associated particles are measured by the ALICE detector in p-Pb collisions at a
nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum
range 0.7 5.0 GeV/ is examined,
to include correlations induced by jets originating from low
momen\-tum-transfer scatterings (minijets). The correlations expressed as
associated yield per trigger particle are obtained in the pseudorapidity range
. The near-side long-range pseudorapidity correlations observed in
high-multiplicity p-Pb collisions are subtracted from both near-side
short-range and away-side correlations in order to remove the non-jet-like
components. The yields in the jet-like peaks are found to be invariant with
event multiplicity with the exception of events with low multiplicity. This
invariance is consistent with the particles being produced via the incoherent
fragmentation of multiple parton--parton scatterings, while the yield related
to the previously observed ridge structures is not jet-related. The number of
uncorrelated sources of particle production is found to increase linearly with
multiplicity, suggesting no saturation of the number of multi-parton
interactions even in the highest multiplicity p-Pb collisions. Further, the
number scales in the intermediate multiplicity region with the number of binary
nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/161
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