Architecture of coatomer: Molecular characterization of delta-COP and protein interactions within the complex

Copyright © 2011 by The Rockefeller University Press.Coatomer is a cytosolic protein complex that forms the coat of COP I-coated transport vesicles. In our attempt to analyze the physical and functional interactions between its seven subunits (coat proteins, [COPs] alpha-zeta), we engaged in a program to clone and characterize the individual coatomer subunits. We have now cloned, sequenced, and overexpressed bovine alpha-COP, the 135-kD subunit of coatomer as well as delta-COP, the 57-kD subunit and have identified a yeast homolog of delta-COP by cDNA sequence comparison and by NH2-terminal peptide sequencing. delta-COP shows homologies to subunits of the clathrin adaptor complexes AP1 and AP2. We show that in Golgi-enriched membrane fractions, the protein is predominantly found in COP I-coated transport vesicles and in the budding regions of the Golgi membranes. A knock-out of the delta-COP gene in yeast is lethal. Immunoprecipitation, as well as analysis exploiting the two-hybrid system in a complete COP screen, showed physical interactions between alpha- and epsilon-COPs and between beta- and delta-COPs. Moreover, the two-hybrid system indicates interactions between gamma- and zeta-COPs as well as between alpha- and beta' COPs. We propose that these interactions reflect in vivo associations of those subunits and thus play a functional role in the assembly of coatomer and/or serve to maintain the molecular architecture of the complex.This work was supported by The Deutsche Forschungsgemeinschaft (SFB 352), the Human Frontier Science Program, and the Swiss National Science Foundation No. 31-43366.95

TCF1(+) hepatitis C virus-specific CD8(+) T cells are maintained after cessation of chronic antigen stimulation.

Differentiation and fate of virus-specific CD8(+) T cells after cessation of chronic antigen stimulation is unclear. Here we show that a TCF1(+)CD127(+)PD1(+) hepatitis C virus (HCV)-specific CD8(+) T-cell subset exists in chronically infected patients with phenotypic features of T-cell exhaustion and memory, both before and after treatment with direct acting antiviral (DAA) agents. This subset is maintained during, and for a long duration after, HCV elimination. After antigen re-challenge the less differentiated TCF1(+)CD127(+)PD1(+) population expands, which is accompanied by emergence of terminally exhausted TCF1-CD127-PD1(hi) HCV-specific CD8(+) T cells. These results suggest the TCF1(+)CD127(+)PD1(+) HCV-specific CD8(+) T-cell subset has memory-like characteristics, including antigen-independent survival and recall proliferation. We thus provide evidence for the establishment of memory-like virus-specific CD8(+) T cells in a clinically relevant setting of chronic viral infection and we uncover their fate after cessation of chronic antigen stimulation, implicating a potential strategy for antiviral immunotherapy

Towards Loop Quantization of Plane Gravitational Waves

The polarized Gowdy model in terms of Ashtekar-Barbero variables is further reduced by including the Killing equations for plane-fronted parallel gravitational waves with parallel rays. The resulting constraint algebra, including one constraint derived from the Killing equations in addition to the standard ones of General Relativity, are shown to form a set of first-class constraints. Using earlier work by Banerjee and Date the constraints are expressed in terms of classical quantities that have an operator equivalent in Loop Quantum Gravity, making space-times with pp-waves accessible to loop quantization techniques.Comment: 14 page

Beyond Einstein-Cartan gravity: Quadratic torsion and curvature invariants with even and odd parity including all boundary terms

Recently, gravitational gauge theories with torsion have been discussed by an increasing number of authors from a classical as well as from a quantum field theoretical point of view. The Einstein-Cartan(-Sciama-Kibble) Lagrangian has been enriched by the parity odd pseudoscalar curvature (Hojman, Mukku, and Sayed) and by torsion square and curvature square pieces, likewise of even and odd parity. (i) We show that the inverse of the so-called Barbero-Immirzi parameter multiplying the pseudoscalar curvature, because of the topological Nieh-Yan form, can only be appropriately discussed if torsion square pieces are included. (ii) The quadratic gauge Lagrangian with both parities, proposed by Obukhov et al. and Baekler et al., emerges also in the framework of Diakonov et al.(2011). We establish the exact relations between both approaches by applying the topological Euler and Pontryagin forms in a Riemann-Cartan space expressed for the first time in terms of irreducible pieces of the curvature tensor. (iii) Only in a Riemann-Cartan spacetime, that is, in a spacetime with torsion, parity violating terms can be brought into the gravitational Lagrangian in a straightforward and natural way. Accordingly, Riemann-Cartan spacetime is a natural habitat for chiral fermionic matter fields.Comment: 12 page latex, as version 2 an old file was submitted by mistake, this is now the real corrected fil

A new study of 25^{25}Mg(α\alpha,n)28^{28}Si angular distributions at EαE_\alpha = 3 - 5 MeV

The observation of $^{26}$Al gives us the proof of active nucleosynthesis in the Milky Way. However the identification of the main producers of $^{26}$Al is still a matter of debate. Many sites have been proposed, but our poor knowledge of the nuclear processes involved introduces high uncertainties. In particular, the limited accuracy on the $^{25}$Mg($\alpha$,n)$^{28}$Si reaction cross section has been identified as the main source of nuclear uncertainty in the production of $^{26}$Al in C/Ne explosive burning in massive stars, which has been suggested to be the main source of $^{26}$Al in the Galaxy. We studied this reaction through neutron spectroscopy at the CN Van de Graaff accelerator of the Legnaro National Laboratories. Thanks to this technique we are able to discriminate the ($\alpha$,n) events from possible contamination arising from parasitic reactions. In particular, we measured the neutron angular distributions at 5 different beam energies (between 3 and 5 MeV) in the \ang{17.5}-\ang{106} laboratory system angular range. The presented results disagree with the assumptions introduced in the analysis of a previous experiment.Comment: 9 pages, 9 figures - accepted by EPJ

Assessing Pulmonary Perfusion in Emphysema Automated Quantification of Perfused Blood Volume in Dual-Energy CTPA

Objectives: The objective of this study was to determine whether automated quantification of lung perfused blood volume (PBV) in dual-energy computed tomographic pulmonary angiography (DE-CTPA) can be used to assess the severity and regional distribution of pulmonary hypoperfusion in emphysema. Materials and Methods: We retrospectively analyzed 40 consecutive patients (mean age, 67 13] years) with pulmonary emphysema, who have no cardiopulmonary comorbidities, and a DE-CTPA negative for pulmonary embolism. Automated quantification of global and regional pulmonary PBV was performed using the syngo Dual Energy application (Siemens Healthcare). Similarly, the global and regional degrees of parenchymal hypodensity were assessed automatically as the percentage of voxels with a computed tomographic density less than -900 Hounsfield unit. Emphysema severity was rated visually, and pulmonary function tests were obtained by chart review, if available. Results: Global PBV generated by automated quantification of pulmonary PBV in the DE-CTPA data sets showed a moderately strong but highly significant negative correlation with residual volume in percentage of the predicted residual volume (r = -0.62; P = 0.002; n = 23) and a positive correlation with forced expiratory volume in 1 second in percentage of the predicted forced expiratory volume in 1 second (r = 0.67; P < 0.001; n = 23). Global PBV values strongly correlated with diffusing lung capacity for carbon monoxide (r = 0.80; P < 0.001; n = 15). Pulmonary PBV values decreased with visual emphysema severity (r = -0.46, P = 0.003, n = 40). Moderate negative correlations were found between global PBV values and parenchymal hypodensity both in a per-patient (r = -0.63; P G 0.001; n = 40) and per-region analyses (r = -0.62; P < 0.001; n = 40). Conclusions: Dual-energy computed tomographic pulmonary angiography allows simultaneous assessment of lung morphology, parenchymal density, and pulmonary PBV. In patients with pulmonary emphysema, automated quantification of pulmonary PBV in DE-CTPA can be used for a quick, reader-independent estimation of global and regional pulmonary perfusion, which correlates with several lung function parameters

Strong Deformation Effects in Hot Rotating 46Ti

Exotic-deformation effects in 46Ti nucleus were investigated by analysing the high-energy gamma-ray and the alpha-particle energy spectra. One of the experiments was performed using the charged-particle multi-detector array ICARE together with a large volume (4"x4") BGO detector. The study focused on simultaneous measurement of light charged particles and gamma-rays in coincidence with the evaporation residues. The experimental data show a signature of very large deformations of the compound nucleus in the Jacobi transition region at the highest spins. These results are compared to data from previous experiments performed with the HECTOR array coupled to the EUROBALL array, where it was found that the GDR strength function is highly fragmented, strongly indicating a presence of nuclei with very large deformation.Comment: 10 pages, 6 figures, Proceedings of the Zakopane Conference on Nuclear Physics, to be published in Acta Phys. Pol. B (2007

Quantum singularity of Levi-Civita spacetimes

Quantum singularities in general relativistic spacetimes are determined by the behavior of quantum test particles. A static spacetime is quantum mechanically singular if the spatial portion of the wave operator is not essentially self-adjoint. Here Weyl's limit point-limit circle criterion is used to determine whether a wave operator is essentially self-adjoint. This test is then applied to scalar wave packets in Levi-Civita spacetimes to help elucidate the physical properties of the spacetimes in terms of their metric parameters

Measurement of gamma p --> K+ Lambda and gamma p --> K+ Sigma0 at photon energies up to 2.6 GeV

The reactions gamma p --> K+ Lambda and gamma p --> K+ Sigma0 were measured in the energy range from threshold up to a photon energy of 2.6 GeV. The data were taken with the SAPHIR detector at the electron stretcher facility, ELSA. Results on cross sections and hyperon polarizations are presented as a function of kaon production angle and photon energy. The total cross section for Lambda production rises steeply with energy close to threshold, whereas the Sigma0 cross section rises slowly to a maximum at about E_gamma = 1.45 GeV. Cross sections together with their angular decompositions into Legendre polynomials suggest contributions from resonance production for both reactions. In general, the induced polarization of Lambda has negative values in the kaon forward direction and positive values in the backward direction. The magnitude varies with energy. The polarization of Sigma0 follows a similar angular and energy dependence as that of Lambda, but with opposite sign.Comment: 21 pages, 25 figures, submitted to Eur. Phys. J.

Loop quantum gravity: the first twenty five years

This is a review paper invited by the journal "Classical ad Quantum Gravity" for a "Cluster Issue" on approaches to quantum gravity. I give a synthetic presentation of loop gravity. I spell-out the aims of the theory and compare the results obtained with the initial hopes that motivated the early interest in this research direction. I give my own perspective on the status of the program and attempt of a critical evaluation of its successes and limits.Comment: 24 pages, 3 figure