A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity To Cholesterol, And Perturbed Interdomain Coupling

Influenza A M2 is a membrane-associated protein with a C-terminal amphipathic helix that plays a cholesterol-dependent role in viral budding. An M2 mutant with alanine substitutions in the C-terminal amphipathic helix is deficient in viral scission. With the goal of providing atomic-level understanding of how the wild-type protein functions, we used a multipronged site-directed spin labeling electron paramagnetic resonance spectroscopy (SDSL-EPR) approach to characterize the conformational properties of the alanine mutant. We spin-labeled sites in the transmembrane (TM) domain and the C-terminal amphipathic helix (AH) of wild-type (WT) and mutant M2, and collected information on line shapes, relaxation rates, membrane topology, and distances within the homotetramer in membranes with and without cholesterol. Our results identify marked differences in the conformation and dynamics between the WT and the alanine mutant. Compared to WT, the dominant population of the mutant AH is more dynamic, shallower in the membrane, and has altered quaternary arrangement of the C-terminal domain. While the AH becomes more dynamic, the dominant population of the TM domain of the mutant is immobilized. The presence of cholesterol changes the conformation and dynamics of the WT protein, while the alanine mutant is insensitive to cholesterol. These findings provide new insight into how M2 may facilitate budding. We propose the AH–membrane interaction modulates the arrangement of the TM helices, effectively stabilizing a conformational state that enables M2 to facilitate viral budding. Antagonizing the properties of the AH that enable interdomain coupling within M2 may therefore present a novel strategy for anti-influenza drug design

Nonlinear Dirac operator and quaternionic analysis

Properties of the Cauchy-Riemann-Fueter equation for maps between quaternionic manifolds are studied. Spaces of solutions in case of maps from a K3-surface to the cotangent bundle of a complex projective space are computed. A relationship between harmonic spinors of a generalized nonlinear Dirac operator and solutions of the Cauchy-Riemann-Fueter equation are established.Comment: Cosmetic changes onl

A direct probe of cosmological power spectra of the peculiar velocity field and the gravitational lensing magnification from photometric redshift surveys

The cosmological peculiar velocity field (deviations from the pure Hubble flow) of matter carries significant information on dark energy, dark matter and the underlying theory of gravity on large scales. Peculiar motions of galaxies introduce systematic deviations between the observed galaxy redshifts z and the corresponding cosmological redshifts z_cos. A novel method for estimating the angular power spectrum of the peculiar velocity field based on observations of galaxy redshifts and apparent magnitudes m (or equivalently fluxes) is presented. This method exploits the fact that a mean relation between z_cos and m of galaxies can be derived from all galaxies in a redshift-magnitude survey. Given a galaxy magnitude, it is shown that the z_cos(m) relation yields its cosmological redshift with a 1-sigma error of sigma_z~0.3 for a survey like Euclid (~10^9 galaxies at z<~2), and can be used to constrain the angular power spectrum of z-z_cos(m) with a high signal-to-noise ratio. At large angular separations corresponding to l<~15, we obtain significant constraints on the power spectrum of the peculiar velocity field. At 15<~l<~60, magnitude shifts in the z_cos(m) relation caused by gravitational lensing magnification dominate, allowing us to probe the line-of-sight integral of the gravitational potential. Effects related to the environmental dependence in the luminosity function can easily be computed and their contamination removed from the estimated power spectra. The amplitude of the combined velocity and lensing power spectra at z~1 can be measured with <~5% accuracy.Comment: 22 pages, 3 figures; added a discussion of systematic errors, accepted for publication in JCA

Long-time discrete particle effects versus kinetic theory in the self-consistent single-wave model

The influence of the finite number N of particles coupled to a monochromatic wave in a collisionless plasma is investigated. For growth as well as damping of the wave, discrete particle numerical simulations show an N-dependent long time behavior resulting from the dynamics of individual particles. This behavior differs from the one due to the numerical errors incurred by Vlasov approaches. Trapping oscillations are crucial to long time dynamics, as the wave oscillations are controlled by the particle distribution inhomogeneities and the pulsating separatrix crossings drive the relaxation towards thermal equilibrium.Comment: 11 pages incl. 13 figs. Phys. Rev. E, in pres

Wall-Crossing in Coupled 2d-4d Systems

We introduce a new wall-crossing formula which combines and generalizes the Cecotti-Vafa and Kontsevich-Soibelman formulas for supersymmetric 2d and 4d systems respectively. This 2d-4d wall-crossing formula governs the wall-crossing of BPS states in an N=2 supersymmetric 4d gauge theory coupled to a supersymmetric surface defect. When the theory and defect are compactified on a circle, we get a 3d theory with a supersymmetric line operator, corresponding to a hyperholomorphic connection on a vector bundle over a hyperkahler space. The 2d-4d wall-crossing formula can be interpreted as a smoothness condition for this hyperholomorphic connection. We explain how the 2d-4d BPS spectrum can be determined for 4d theories of class S, that is, for those theories obtained by compactifying the six-dimensional (0,2) theory with a partial topological twist on a punctured Riemann surface C. For such theories there are canonical surface defects. We illustrate with several examples in the case of A_1 theories of class S. Finally, we indicate how our results can be used to produce solutions to the A_1 Hitchin equations on the Riemann surface C.Comment: 170 pages, 45 figure

The 6dF Galaxy Survey: bulk flows on 50-70 h

We measure the bulk flow of the local Universe using the 6dF Galaxy Survey peculiar velocity sample (6dFGSv), the largest and most homogeneous peculiar velocity sample to date. 6dFGSv is a Fundamental Plane sample of ∼104 peculiar velocities covering the whole Southern hemisphere for galactic latitude |b| > 10°, out to redshift z = 0.0537. We apply the ‘minimum variance’ bulk flow weighting method, which allows us to make a robust measurement of the bulk flow on scales of 50 and 70 h−1 Mpc. We investigate and correct for potential bias due to the lognormal velocity uncertainties, and verify our method by constructing Λ cold dark matter (ΛCDM) 6dFGSv mock catalogues incorporating the survey selection function. For a hemisphere of radius 50 h−1 Mpc we find a bulk flow amplitude of U = 248 ± 58 km s−1 in the direction (l, b) = (318° ± 20°, 40° ± 13°), and for 70 h−1 Mpc we find U = 243 ± 58 km s−1, in the same direction. Our measurement gives us a constraint on σ8 of 1.01+1.07−0.58. Our results are in agreement with other recent measurements of the direction of the bulk flow, and our measured amplitude is consistent with a ΛCDM prediction

Strong lensing probability in TeVeS theory

We recalculate the strong lensing probability as a function of the image separation in TeVeS (tensor-vector-scalar) cosmology, which is a relativistic version of MOND (MOdified Newtonian Dynamics). The lens is modeled by the Hernquist profile. We assume an open cosmology with $\Omega_b=0.04$ and $\Omega_\Lambda=0.5$ and three different kinds of interpolating functions. Two different galaxy stellar mass functions (GSMF) are adopted: PHJ (Panter-Heavens-Jimenez, 2004) determined from SDSS data release one and Fontana (Fontana et al., 2006) from GOODS-MUSIC catalog. We compare our results with both the predicted probabilities for lenses by Singular Isothermal Sphere (SIS) galaxy halos in LCDM (lambda cold dark matter) with Schechter-fit velocity function, and the observational results of the well defined combined sample of Cosmic Lens All-Sky Survey (CLASS) and Jodrell Bank/Very Large Array Astrometric Survey (JVAS). It turns out that the interpolating function $\mu(x)=x/(1+x)$ combined with Fontana GSMF matches the results from CLASS/JVAS quite well.Comment: 15 pages, 3 figures, 1 table. Published in JCA

Visuospatial Integration: Paleoanthropological and Archaeological Perspectives

The visuospatial system integrates inner and outer functional processes, organizing spatial, temporal, and social interactions between the brain, body, and environment. These processes involve sensorimotor networks like the eye–hand circuit, which is especially important to primates, given their reliance on vision and touch as primary sensory modalities and the use of the hands in social and environmental interactions. At the same time, visuospatial cognition is intimately connected with memory, self-awareness, and simulation capacity. In the present article, we review issues associated with investigating visuospatial integration in extinct human groups through the use of anatomical and behavioral data gleaned from the paleontological and archaeological records. In modern humans, paleoneurological analyses have demonstrated noticeable and unique morphological changes in the parietal cortex, a region crucial to visuospatial management. Archaeological data provides information on hand–tool interaction, the spatial behavior of past populations, and their interaction with the environment. Visuospatial integration may represent a critical bridge between extended cognition, self-awareness, and social perception. As such, visuospatial functions are relevant to the hypothesis that human evolution is characterized by changes in brain–body–environment interactions and relations, which enhance integration between internal and external cognitive components through neural plasticity and the development of a specialized embodiment capacity. We therefore advocate the investigation of visuospatial functions in past populations through the paleoneurological study of anatomical elements and archaeological analysis of visuospatial behaviors