Ammonites from the Lower Bajocian (Middle Jurassic) beds of the classic locality of Bakonycsernye (Transdanubian Hungary), with special regard to the early otoitids and stephanoceratids

New collecting from the Middle Jurassic beds of the classic Bakonycsernye locality yielded very rich ammonite assemblages from the topmost Aalenian and the Lower Bajocian. A single bed, called here the Ovale Bed gave a high diversity Fissilobiceras ovale Zone fauna, with several stratigraphically diagnostic species and rich representation of early otoitids and stephanoceratids. These latters include topotypes of species described in classic monographs from this place. Here the earliest otoitids and stephanoceratids, Docidoceras wysogorskii and Westermannites chocsinskyi, respectively, appear first in beds belonging into the Graphoceras concavum Zone. The type horizon of W. telegdirothi, the best-known stephanoceratid from Csernye, most probably is within the Hyperlioceras discites Zone. Two new species are described, the otoitid Trilobiticeras (Emileites) kecskemetii n.sp. and the stephanoceratid Mollistephanus ottiliae n.sp., both form the Ovale Bed. Faunal affinities and the early development of the Otoitidae and Stephanoceratidae are discussed.Neubesammlungen der mitteljurassischen Schichten der klassischen Bakonycsernye Lokalität haben reiche Ammonitenvergesellschaftungen aus dem obersten Aalenium und unteren Bajocium erbracht. Aus einer Schicht, welche hier als Ovale Schicht bezeichnet wird, stammt eine diverse Fissilobiceras ovale Zone Fauna, die gleich mehrere stratigraphisch wichtige Taxa sowie frühe Otoitiden und Stephanoceratiden enthält. Letztere beinhalten Topotypen von Arten, die bereits in den klassischen Monoraphien über die Lokalität beschrieben wurden. Die frühesten Vertreter der Otoitiden und Stephanoceratiden, Docidoceras wysogorskii bzw. Westermannites chocsinskyi, erscheinen erstmalig in Schichten, die zur Graphoceras concavum Zone gehören. Der Typushorizont von W. telegdirothi, die am besten bekannte Stephanoceratidenart von Csernye, liegt sehr wahrscheinlich innerhalb der Hyperlioceras discites Zone. Zwei neue Taxa werden beschrieben, zum einen der Otoitide Trilobiticeras (Emileites) kecskemetii n. sp., zum anderen der Stephanoceratide Mollistephanus ottiliae n. sp. Beide stammen aus der Ovale Schicht. Die faunistischen Beziehungen sowie die frühe Entwicklung der Otoitidae und Stephanoceratidae werden diskutiert

3D architecture of DNA Pol α reveals the functional core of multi-subunit replicative polymerases

Eukaryotic DNA replication requires the coordinated activity of the multi-subunit DNA polymerases: Pol α, Pol δ and Pol ɛ. The conserved catalytic and regulatory B subunits associate in a constitutive heterodimer that represents the functional core of all three replicative polymerases. Here, we combine X-ray crystallography and electron microscopy (EM) to describe subunit interaction and 3D architecture of heterodimeric yeast Pol α. The crystal structure of the C-terminal domain (CTD) of the catalytic subunit bound to the B subunit illustrates a conserved mechanism of accessory factor recruitment by replicative polymerases. The EM reconstructions of Pol α reveal a bilobal shape with separate catalytic and regulatory modules. Docking of the B–CTD complex in the EM reconstruction shows that the B subunit is tethered to the polymerase domain through a structured but flexible linker. Our combined findings provide a structural template for the common functional architecture of the three major replicative DNA polymerases

The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

International audienceWe recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps

Transient Protein-Protein Interaction of the SH3-Peptide Complex via Closely Located Multiple Binding Sites

Protein-protein interactions play an essential role in cellular processes. Certain proteins form stable complexes with their partner proteins, whereas others function by forming transient complexes. The conventional protein-protein interaction model describes an interaction between two proteins under the assumption that a protein binds to its partner protein through a single binding site. In this study, we improved the conventional interaction model by developing a Multiple-Site (MS) model in which a protein binds to its partner protein through closely located multiple binding sites on a surface of the partner protein by transiently docking at each binding site with individual binding free energies. To test this model, we used the protein-protein interaction mediated by Src homology 3 (SH3) domains. SH3 domains recognize their partners via a weak, transient interaction and are therefore promiscuous in nature. Because the MS model requires large amounts of data compared with the conventional interaction model, we used experimental data from the positionally addressable syntheses of peptides on cellulose membranes (SPOT-synthesis) technique. From the analysis of the experimental data, individual binding free energies for each binding site of peptides were extracted. A comparison of the individual binding free energies from the analysis with those from atomistic force fields gave a correlation coefficient of 0.66. Furthermore, application of the MS model to 10 SH3 domains lowers the prediction error by up to 9% compared with the conventional interaction model. This improvement in prediction originates from a more realistic description of complex formation than the conventional interaction model. The results suggested that, in many cases, SH3 domains increased the protein complex population through multiple binding sites of their partner proteins. Our study indicates that the consideration of general complex formation is important for the accurate description of protein complex formation, and especially for those of weak or transient protein complexes

PEG-capped, lanthanide doped GdF3 nanoparticles: luminescent and T-2 contrast agents for optical and MRI multimodal imaging

A facile method for the synthesis of water dispersible Er3+/Yb3+ and Tm3+/Yb3+ doped upconverting GdF3 nanoparticles is reported. Strong upconversion emissions are observed in the red (for Er/Yb doped) and near-infrared (for Tm/Yb doped) regions upon laser excitation at 980 nm. The PEG coating ensures a good dispersion of the system in water and reduces the radiationless de-excitation of the excited states of the Er3+ and Tm3+ ions by water molecules. The r(2) relaxivity values are quite high with respect to the common T-2-relaxing agents (22.6 +/- 3.4 mM(-1) s(-1) and 15.8 +/- 3.4 mM(-1) s(-1) for the Tm/Yb and Er/Yb doped samples, respectively), suggesting that the present NPs can be interesting as T-2 weighted contrast agents for proton MRI purpose. Preliminary experiments conducted in vitro, in stem cell cultures, and in vivo, after subcutaneous injection of the lanthanide-doped GdF3 NPs, indicate scarce toxic effects. After an intravenous injection in mice, the GdF3 NPs localize mainly in the liver. The present results indicate that the present Er3+/Yb3+ and Tm3+/Yb3+ doped GdF3 NPs are suitable candidates to be efficiently used as bimodal probes for both in vitro and in vivo optical and magnetic resonance imaging