Divalent Metal Ion Coordination by Residue T118 of Anthrax Toxin Receptor 2 Is Not Essential for Protective Antigen Binding

The protective antigen (PA) subunit of anthrax toxin interacts with the integrin-like I domains of either of two cellular receptors, ANTXR1 or ANTXR2. These I domains contain a metal ion-dependent adhesion site (MIDAS) made up of five non-consecutive amino acid residues that coordinate a divalent metal ion that is important for PA-binding. The MIDAS residues of integrin I domains shift depending upon whether the domain exists in a closed (ligand-unbound) or open (ligand-bound) conformation. Of relevance to this study, the MIDAS threonine residue coordinates the metal ion only in the open I domain conformation. Previously it was shown that the MIDAS threonine is essential for PA interaction with ANTXR1, a result consistent with the requirement that the I domain of that receptor adopts an open conformation for PA-binding [1]. Here we have tested the requirement for the MIDAS threonine of ANTXR2 for PA-binding. We show that the toxin can bind to a mutant receptor lacking the MIDAS threonine and that it can use that mutant receptor to intoxicate cultured cells. These findings suggest that an open-like configuration of the ANTXR2 MIDAS is not essential for the interaction with PA

Plasticity and learning in a network of coupled phase oscillators

A generalized Kuramoto model of coupled phase oscillators with slowly varying coupling matrix is studied. The dynamics of the coupling coefficients is driven by the phase difference of pairs of oscillators in such a way that the coupling strengthens for synchronized oscillators and weakens for non-synchronized pairs. The system possesses a family of stable solutions corresponding to synchronized clusters of different sizes. A particular cluster can be formed by applying external driving at a given frequency to a group of oscillators. Once established, the synchronized state is robust against noise and small variations in natural frequencies. The phase differences between oscillators within the synchronized cluster can be used for information storage and retrieval.Comment: 10 page

Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation

The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH ∼6.0 or below when it is bound to ANTXR1, but only at pH ∼5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation

Atenolol versus losartan in children and young adults with Marfan's syndrome

BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

The Effects of Atmospheric Dispersion on High-Resolution Solar Spectroscopy

We investigate the effects of atmospheric dispersion on observations of the Sun at the ever-higher spatial resolutions afforded by increased apertures and improved techniques. The problems induced by atmospheric refraction are particularly significant for solar physics because the Sun is often best observed at low elevations, and the effect of the image displacement is not merely a loss of efficiency, but the mixing of information originating from different points on the solar surface. We calculate the magnitude of the atmospheric dispersion for the Sun during the year and examine the problems produced by this dispersion in both spectrographic and filter observations. We describe an observing technique for scanning spectrograph observations that minimizes the effects of the atmospheric dispersion while maintaining a regular scanning geometry. Such an approach could be useful for the new class of high-resolution solar spectrographs, such as SPINOR, POLIS, TRIPPEL, and ViSP

Vortex states in 2D superconductor at high magnetic field in a periodic pinning potential

The effect of a periodic pinning array on the vortex state in a 2D superconductor at low temperatures is studied within the framework of the Ginzburg-Landau approach. It is shown that attractive interaction of vortex cores to a commensurate pin lattice stabilizes vortex solid phases with long range positional order against violent shear fluctuations. Exploiting a simple analytical method, based on the Landau orbitals description, we derive a rather detailed picture of the low temperatures vortex state phase diagram. It is predicted that for sufficiently clean samples application of an artificial periodic pinning array would enable one to directly detect the intrinsic shear stiffness anisotropy characterizing the ideal vortex lattice.Comment: 8 pages, 5 figure

Properties of the random field Ising model in a transverse magnetic field

We consider the effect of a random longitudinal field on the Ising model in a transverse magnetic field. For spatial dimension $d > 2$, there is at low strength of randomness and transverse field, a phase with true long range order which is destroyed at higher values of the randomness or transverse field. The properties of the quantum phase transition at zero temperature are controlled by a fixed point with no quantum fluctuations. This fixed point also controls the classical finite temperature phase transition in this model. Many critical properties of the quantum transition are therefore identical to those of the classical transition. In particular, we argue that the dynamical scaling is activated, i.e, the logarithm of the diverging time scale rises as a power of the diverging length scale

An ultrafast x-ray detector system at an elliptically polarizingundulator beamline

An ultrafast x-ray detector system is under development atLawrence Berkeley National Laboratory (LBNL) for application primarily tostudyies of ultrafast magnetization dynamics. The system consists of a fslaser, an x-ray streak camera and an ellipitically polarization undulator(EPU) beamline. Polarized x-rays from an EPU can be used to measure x-raymagnetic circular dichroism (XMCD) of a sample. XMCD has the uniqueability to independently measure orbit and spin magnetization withsub-monolayer sensitivity and element specificity. The streak camera hassimultaneously a sub-picosecond temporal resolution and a high spatialresolution. The combination of the streak camera and EPU allows us tostudy the transfer of angular momentum from spin to orbit to the latticein the sample on an ultrafast time scale. We describe here theperformance of the ultrafast detector, the laser and the x-raysynchronization system. The observation of the demagnetization process ofdifferent samples demonstrates the ability of the apparatus

Altered expression of microRNA-451 in eutopic endometrium of baboons ( Papio anubis ) with endometriosis

Are microRNAs (miRs) altered in the eutopic endometrium (EuE) of baboons following the induction of endometriosis