Molecular Basis of Lysosomal Enzyme Recognition: Three-Dimensional Structure of the Cation-Dependent Mannose 6-Phosphate Receptor

AbstractTargeting of newly synthesized lysosomal hydrolases to the lysosome is mediated by the cation-dependent mannose 6-phosphate receptor (CD-MPR) and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor (IGF-II/CI-MPR). The two receptors, which share sequence similarities, constitute the P-type family of animal lectins. We now report the three-dimensional structure of a glycosylation-deficient, yet fully functional form of the extracytoplasmic domain of the bovine CD-MPR (residues 3–154) complexed with mannose 6-phosphate at 1.8 Å resolution. The extracytoplasmic domain of the CD-MPR crystallizes as a dimer, and each monomer folds into a nine-stranded flattened β barrel, which bears a striking resemblance to avidin. The distance of 40 Å between the two ligand-binding sites of the dimer provides a structural basis for the observed differences in binding affinity exhibited by the CD-MPR toward various lysosomal enzymes

Symmetry-breaking transitions in networks of nonlinear circuit elements

We investigate a nonlinear circuit consisting of N tunnel diodes in series, which shows close similarities to a semiconductor superlattice or to a neural network. Each tunnel diode is modeled by a three-variable FitzHugh-Nagumo-like system. The tunnel diodes are coupled globally through a load resistor. We find complex bifurcation scenarios with symmetry-breaking transitions that generate multiple fixed points off the synchronization manifold. We show that multiply degenerate zero-eigenvalue bifurcations occur, which lead to multistable current branches, and that these bifurcations are also degenerate with a Hopf bifurcation. These predicted scenarios of multiple branches and degenerate bifurcations are also found experimentally.Comment: 32 pages, 11 figures, 7 movies available as ancillary file

Synchronisation in networks of delay-coupled type-I excitable systems

We use a generic model for type-I excitability (known as the SNIPER or SNIC model) to describe the local dynamics of nodes within a network in the presence of non-zero coupling delays. Utilising the method of the Master Stability Function, we investigate the stability of the zero-lag synchronised dynamics of the network nodes and its dependence on the two coupling parameters, namely the coupling strength and delay time. Unlike in the FitzHugh-Nagumo model (a model for type-II excitability), there are parameter ranges where the stability of synchronisation depends on the coupling strength and delay time. One important implication of these results is that there exist complex networks for which the adding of inhibitory links in a small-world fashion may not only lead to a loss of stable synchronisation, but may also restabilise synchronisation or introduce multiple transitions between synchronisation and desynchronisation. To underline the scope of our results, we show using the Stuart-Landau model that such multiple transitions do not only occur in excitable systems, but also in oscillatory ones.Comment: 10 pages, 9 figure

Heavy-flavour and quarkonium production in the LHC era: from proton-proton to heavy-ion collisions

This report reviews the study of open heavy-flavour and quarkonium production in high-energy hadronic collisions, as tools to investigate fundamental aspects of Quantum Chromodynamics, from the proton and nucleus structure at high energy to deconfinement and the properties of the Quark-Gluon Plasma. Emphasis is given to the lessons learnt from LHC Run 1 results, which are reviewed in a global picture with the results from SPS and RHIC at lower energies, as well as to the questions to be addressed in the future. The report covers heavy flavour and quarkonium production in proton-proton, proton-nucleus and nucleus-nucleus collisions. This includes discussion of the effects of hot and cold strongly interacting matter, quarkonium photo-production in nucleus-nucleus collisions and perspectives on the study of heavy flavour and quarkonium with upgrades of existing experiments and new experiments. The report results from the activity of the SaporeGravis network of the I3 Hadron Physics programme of the European Union 7th Framework Programme

The response of perennial and temporary headwater stream invertebrate communities to hydrological extremes

The headwaters of karst rivers experience considerable hydrological variability, including spates and streambed drying. Extreme summer flooding on the River Lathkill (Derbyshire, UK) provided the opportunity to examine the invertebrate community response to unseasonal spate flows, flow recession and, at temporary sites, streambed drying. Invertebrates were sampled at sites with differing flow permanence regimes during and after the spates. Following streambed drying at temporary sites, dewatered surface sediments were investigated as a refugium for aquatic invertebrates. Experimental rehydration of these dewatered sediments was conducted to promote development of desiccation-tolerant life stages. At perennial sites, spate flows reduced invertebrate abundance and diversity, whilst at temporary sites, flow reactivation facilitated rapid colonisation of the surface channel by a limited number of invertebrate taxa. Following streambed drying, 38 taxa were recorded from the dewatered and rehydrated sediments, with Oligochaeta being the most abundant taxon and Chironomidae (Diptera) the most diverse. Experimental rehydration of dewatered sediments revealed the presence of additional taxa, including Stenophylax sp. (Trichoptera: Limnephilidae) and Nemoura sp. (Plecoptera: Nemouridae). The influence of flow permanence on invertebrate community composition was apparent despite the aseasonal high-magnitude flood events

Inclusive cross section and double helicity asymmetry for pi^0 production in p+p collisions at sqrt(s) = 62.4 GeV

The PHENIX experiment presents results from the RHIC 2006 run with polarized proton collisions at sqrt(s) = 62.4 GeV for inclusive pi^0 production at mid-rapidity. Unpolarized cross section results are measured for transverse momenta p_T = 0.5 to 7 GeV/c. Next-to-leading order perturbative quantum chromodynamics calculations are compared with the data, and while the calculations are consistent with the measurements, next-to-leading logarithmic corrections improve the agreement. Double helicity asymmetries A_LL are presented for p_T = 1 to 4 GeV/c and probe the higher range of Bjorken_x of the gluon (x_g) with better statistical precision than our previous measurements at sqrt(s)=200 GeV. These measurements are sensitive to the gluon polarization in the proton for 0.06 < x_g < 0.4.Comment: 387 authors from 63 institutions, 10 pages, 6 figures, 1 table. Submitted to Physical Review D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Charged hadron multiplicity fluctuations in Au+Au and Cu+Cu collisions from sqrt(s_NN) = 22.5 to 200 GeV

A comprehensive survey of event-by-event fluctuations of charged hadron multiplicity in relativistic heavy ions is presented. The survey covers Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV, and Cu+Cu collisions sqrt(s_NN) = 22.5, 62.4, and 200 GeV. Fluctuations are measured as a function of collision centrality, transverse momentum range, and charge sign. After correcting for non-dynamical fluctuations due to fluctuations in the collision geometry within a centrality bin, the remaining dynamical fluctuations expressed as the variance normalized by the mean tend to decrease with increasing centrality. The dynamical fluctuations are consistent with or below the expectation from a superposition of participant nucleon-nucleon collisions based upon p+p data, indicating that this dataset does not exhibit evidence of critical behavior in terms of the compressibility of the system. An analysis of Negative Binomial Distribution fits to the multiplicity distributions demonstrates that the heavy ion data exhibit weak clustering properties.Comment: 464 authors from 60 institutions, 17 pages, 12 figures, 1 table. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Quantitative Constraints on the Transport Properties of Hot Partonic Matter from Semi-Inclusive Single High Transverse Momentum Pion Suppression in Au+Au collisions at sqrt(s_NN) = 200 GeV

The PHENIX experiment has measured the suppression of semi-inclusive single high transverse momentum pi^0's in Au+Au collisions at sqrt(s_NN) = 200 GeV. The present understanding of this suppression is in terms of energy-loss of the parent (fragmenting) parton in a dense color-charge medium. We have performed a quantitative comparison between various parton energy-loss models and our experimental data. The statistical point-to-point uncorrelated as well as correlated systematic uncertainties are taken into account in the comparison. We detail this methodology and the resulting constraint on the model parameters, such as the initial color-charge density dN^g/dy, the medium transport coefficient , or the initial energy-loss parameter epsilon_0. We find that high transverse momentum pi^0 suppression in Au+Au collisions has sufficient precision to constrain these model dependent parameters at the +/1 20%-25% (one standard deviation) level. These constraints include only the experimental uncertainties, and further studies are needed to compute the corresponding theoretical uncertainties.Comment: 422 authors, 13 pages text, RevTeX-4, 9 figures, 2 tables. This version is updated with changes made during the review process and is now the same as what was published in Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/papers.htm

Cross sections and double-helicity asymmetries of midrapidity inclusive charged hadrons in p+p collisions at sqrt(s)=62.4 GeV

Unpolarized cross sections and double-helicity asymmetries of single-inclusive positive and negative charged hadrons at midrapidity from p+p collisions at sqrt(s)=62.4 GeV are presented. The PHENIX measurements for 1.0 < p_T < 4.5 GeV/c are consistent with perturbative QCD calculations at next-to-leading order in the strong coupling constant, alpha_s. Resummed pQCD calculations including terms with next-to-leading-log accuracy, yielding reduced theoretical uncertainties, also agree with the data. The double-helicity asymmetry, sensitive at leading order to the gluon polarization in a momentum-fraction range of 0.05 ~< x_gluon ~< 0.2, is consistent with recent global parameterizations disfavoring large gluon polarization.Comment: PHENIX Collaboration. 447 authors, 12 pages, 5 figures, 5 tables. Submitted to Physical Review