67 research outputs found
Morphology of Marburg Virus NPâRNA
AbstractWhen Marburg virus (MBGV) nucleoprotein (NP) is expressed in insect cells, it binds to cellular RNA and forms NPâRNA complexes such as insect cell-expressed nucleoproteins from other nonsegmented negative-strand RNA viruses. Recombinant MBGV NPâRNA forms loose coils that resemble rabies virus NâRNA. MBGV NP monomers are rods that are spaced along the coil similar to the nucleoprotein monomers of the rabies virus NâRNA. High salt treatment induces tight coiling of the MBGV NPâRNA, again a characteristic observed for other nonsegmented negative-strand virus NâRNAs. Electron microscopy of fixed Marburg virus particles shows that the viral nucleocapsid has a smaller diameter than the free, recombinant NPâRNA. This difference in helical parameters could be caused by the interaction of other viral proteins with the NPâRNA. A similar but opposite phenomenon is observed for rhabdovirus nucleocapsids that are condensed by the viral matrix protein upon which they acquire a larger diameter. Finally, there appears to be an extensive and regular protein scaffold between the viral nucleocapsid and the membrane that seems not to exist in the other negative-strand RNA viruses
The Spectral Action for Dirac Operators with skew-symmetric Torsion
We derive a formula for the gravitational part of the spectral action for
Dirac operators on 4-dimensional manifolds with totally anti-symmetric torsion.
We find that the torsion becomes dynamical and couples to the traceless part of
the Riemann curvature tensor. Finally we deduce the Lagrangian for the Standard
Model of particle physics in presence of torsion from the Chamseddine-Connes
Dirac operator.Comment: Longer introduction and conclusion adde
Chiral Asymmetry and the Spectral Action
We consider orthogonal connections with arbitrary torsion on compact
Riemannian manifolds. For the induced Dirac operators, twisted Dirac operators
and Dirac operators of Chamseddine-Connes type we compute the spectral action.
In addition to the Einstein-Hilbert action and the bosonic part of the Standard
Model Lagrangian we find the Holst term from Loop Quantum Gravity, a coupling
of the Holst term to the scalar curvature and a prediction for the value of the
Barbero-Immirzi parameter
Pairing, Charge, and Spin Correlations in the Three-Band Hubbard Model
Using the Constrained Path Monte Carlo (CPMC) method, we simulated the
two-dimensional, three-band Hubbard model to study pairing, charge, and spin
correlations as a function of electron and hole doping and the Coulomb
repulsion between charges on neighboring Cu and O lattice sites. As a
function of distance, both the -wave and extended s-wave pairing
correlations decayed quickly. In the charge-transfer regime, increasing
decreased the long-range part of the correlation functions in both
channels, while in the mixed-valent regime, it increased the long-range part of
the s-wave behavior but decreased that of the d-wave behavior. Still the d-wave
behavior dominated. At a given doping, increasing increased the
spin-spin correlations in the charge-transfer regime but decreased them in the
mixed-valent regime. Also increasing suppressed the charge-charge
correlations between neighboring Cu and O sites. Electron and hole doping away
from half-filling was accompanied by a rapid suppression of anti-ferromagnetic
correlations.Comment: Revtex, 8 pages with 15 figure
Ground state of the three-band Hubbard model
The ground state of the two-dimensional three-band Hubbard model in oxide
superconductors is investigated by using the variational Monte Carlo method.
The Gutzwiller-projected BCS and spin- density wave (SDW) functions are
employed in the search for a possible ground state with respect to dependences
on electron density. Antiferromagnetic correlations are considerably enhanced
near half-filling. It is shown that the d-wave state may exist away from
half-filling for both the hole and electron doping cases. The overall structure
of the phase diagram obtained by the calculations qualitatively agrees with
experimental indications. The superconducting condensation energy is in
reasonable agreement with the experimental value obtained from specific heat
and critical magnetic field measurements for optimally doped samples. The
inhomogeneous SDW state is also examined near 1/8-hole doping.Comment: 10 pages, 17 figure
Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia
Air way surface dehydration is a pathological feature of cystic fibrosis (CF) lung disease. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR), a cyclic AMP-regulated Cl- channel controlled in part by the adenosine A2B receptor. An alternative CFTR-independent mechanism of fluid secretion is regulated by ATP via the P2Y2 receptor (P2Y2R) that activates Ca2+-regulated Cl- channels (CaCC/TMEM16) and inhibits Na+ absorption. However, due to rapid ATP hydrolysis, steady-state ATP levels in CF airway surface liquid (ASL) are inadequate to maintain P2Y2Rmediated fluid secretion. Therefore, inhibiting airway epithelial ecto-ATPases to increase ASL ATP levels constitutes a strategy to restore airway surface hydration in CF. Using [Îł32P]ATP as radiotracer, we assessed the effect of a series of ATPase inhibitory compounds on the stability of physiologically occurring ATP concentrations. We identified the polyoxometalate [Co4(H2O)2(PW9O34)2]10- (POM-5) as the most potent and effective ecto-ATPase inhibitor in CF airway epithelial cells. POM-5 caused long-lasting inhibition of ATP hydrolysis in airway epithelia, which was reversible upon removal of the inhibitor. Importantly, POM-5 markedly enhanced steady-state levels of released ATP, promoting increased ASL volume in CF cell surfaces. These results provide proof of concept for ecto-ATPase inhibitors as therapeutic agents to restore hydration of CF airway surfaces. As a test of this notion, cell-free sputum supernatants from CF subjects were studied and found to have abnormally elevated ATPase activity, which was markedly inhibited by POM-5
The Polygenic and Monogenic Basis of Blood Traits and Diseases
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases
Exome Sequencing and Rare Variant Analysis Reveals Multiple Filaggrin Mutations in Bangladeshi Families with Atopic Eczema and Additional Risk Genes
M.P was supported by a Fellowship from the German Research Foundation (DFG).
This work received infrastructure support through the DFG Cluster of Excellence
âInflammation at Interfacesâ (grants EXC306 and EXC306/2), and was supported by grants
(WE2678/6-1, WE2678/6-2, WE2678/9) from the DFG and the e:Med sysINFLAME grant
no. 01ZX1306A from the German Federal Ministry of Education and Research (BMBF).
J.E.A.C. and X.F.C.C.W. are funded by A*STAR SPF funding for translational skin research
and genetic orphan disease
Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia
Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 Ă 10â41) and in 1690 AA subjects (rs505102; P = 1.05 Ă 10â8). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P = 5.21 Ă 10â12; rs35897051, P = 3.32 Ă 10â8). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P = 2.94 Ă 10â12), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a caseâcontrol analysis of âŒ80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study
A MODEST review
We present an account of the state of the art in the fields explored by the
research community invested in 'Modeling and Observing DEnse STellar systems'.
For this purpose, we take as a basis the activities of the MODEST-17
conference, which was held at Charles University, Prague, in September 2017.
Reviewed topics include recent advances in fundamental stellar dynamics,
numerical methods for the solution of the gravitational N-body problem,
formation and evolution of young and old star clusters and galactic nuclei,
their elusive stellar populations, planetary systems, and exotic compact
objects, with timely attention to black holes of different classes of mass and
their role as sources of gravitational waves.
Such a breadth of topics reflects the growing role played by collisional
stellar dynamics in numerous areas of modern astrophysics. Indeed, in the next
decade, many revolutionary instruments will enable the derivation of positions
and velocities of individual stars in the Milky Way and its satellites and will
detect signals from a range of astrophysical sources in different portions of
the electromagnetic and gravitational spectrum, with an unprecedented
sensitivity. On the one hand, this wealth of data will allow us to address a
number of long-standing open questions in star cluster studies; on the other
hand, many unexpected properties of these systems will come to light,
stimulating further progress of our understanding of their formation and
evolution.Comment: 42 pages; accepted for publication in 'Computational Astrophysics and
Cosmology'. We are much grateful to the organisers of the MODEST-17
conference (Charles University, Prague, September 2017). We acknowledge the
input provided by all MODEST-17 participants, and, more generally, by the
members of the MODEST communit
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