Helical Density Research Articles

Bacteria‐Assisted Activation of Antimicrobial Polypeptides by a Random‐Coil to Helix Transition

AbstractThe application of antimicrobial peptides (AMPs) is largely hindered by their non‐specific toxicity against mammalian cells, which is usually associated with helical structure, hydrophobicity, and charge density. A random coil‐to‐helix transition mechanism has now been introduced into the design of AMPs, minimizing the toxicity against mammalian cells while maintaining high antimicrobial activity. By incorporating anionic phosphorylated tyrosine into the cationic polypeptide, the helical structure of AMPs was distorted owing to the side‐chain charge interaction. Together with the decreased charge density, the AMPs exhibited inhibited toxicity against mammalian cells. At the infectious site, the AMPs can be activated by bacterial phosphatase to restore the helical structure, thus contributing to strong membrane disruptive capability and potent antimicrobial activity. This bacteria‐activated system is an effective strategy to enhance the therapeutic selectivity of AMPs.

Bacteria-Assisted Activation of Antimicrobial Polypeptides by a Random-Coil to Helix Transition.

The application of antimicrobial peptides (AMPs) is largely hindered by their non-specific toxicity against mammalian cells, which is usually associated with helical structure, hydrophobicity, and charge density. A random coil-to-helix transition mechanism has now been introduced into the design of AMPs, minimizing the toxicity against mammalian cells while maintaining high antimicrobial activity. By incorporating anionic phosphorylated tyrosine into the cationic polypeptide, the helical structure of AMPs was distorted owing to the side-chain charge interaction. Together with the decreased charge density, the AMPs exhibited inhibited toxicity against mammalian cells. At the infectious site, the AMPs can be activated by bacterial phosphatase to restore the helical structure, thus contributing to strong membrane disruptive capability and potent antimicrobial activity. This bacteria-activated system is an effective strategy to enhance the therapeutic selectivity of AMPs.

UNC5C variants are associated with cerebral amyloid angiopathy.

Objective:To determine whether common genetic variants in UNC5C, a recently identified late-onset Alzheimer disease (LOAD) dementia susceptibility gene, are associated with AD susceptibility or AD-related clinical/pathologic phenotypes.Methods:We used data from deceased individuals of European descent who participated in the Religious Orders Study or the Rush Memory and Aging Project (n = 1,288). We examined whether there were associations between single nucleotide polymorphisms (SNPs) within ±100 kb of the UNC5C gene and a diagnosis of AD dementia, global cognitive decline, a pathologic diagnosis of AD, β-amyloid load, neuritic plaque count, diffuse plaque count, paired helical filament tau density, neurofibrillary tangle count, and cerebral amyloid angiopathy (CAA) score. We also evaluated the relation of the CAA-associated variant and dorsolateral prefrontal cortex (DLPFC) UNC5C RNA expression. Secondary analyses were performed to examine the interaction of the CAA-associated SNP and known genetic risk factors of CAA as well as the association of the SNP with other cerebrovascular pathologies.Results:A set of UNC5C SNPs tagged by rs28660566T was associated with a higher CAA score (p = 2.3 × 10−6): each additional rs28660566T allele was associated with a 0.60 point higher CAA score, which is equivalent to approximately 75% of the higher CAA score associated with each allele of APOE ε4. rs28660566T was weakly associated with lower UNC5C expression in the human DLPFC (p = 0.036). Moreover, rs28660566T had a synergistic interaction with APOE ε4 on their association with higher CAA severity (p = 0.027) and was associated with more severe arteriolosclerosis (p = 0.0065).Conclusions:Targeted analysis of the UNC5C region uncovered a set of SNPs associated with CAA.

μSR study of stoichiometric NbFe2

The magnetic ground state of nominally stoichiometric single crystalline NbFe2 is investigated by bulk magnetisation and muon spin relaxation techniques. Magnetic order clearly emerges below the critical temperature TN=10.3K and is dominated by randomly orientated quasi-static moments. The local field distribution observed by muons can be explained by the phenomenological Gaussian-broadened-Gaussian Kubo Toyabe relaxation function. The observed short range order could be used to describe a new magnetic ground state, but a helical spin density wave with an incommensurate amplitude modulation cannot be ruled out. The sensitivity of μSR to the local magnetic field distribution in the vicinity of the quantum critical point (QCP) in NbFe2 is clearly demonstrated via comparison with already published work. This suggests detailed measurements of the muon relaxation as the QCP is approached will reveal further details of the field distribution and fluctuations in Nb1−yFe2+y.

Manipulating Magneto-Optic Properties of a Chiral Polymer by Doping with Stable Organic Biradicals.

We report the first example of tuning the large magneto-optic activity of a chiral polymer by addition of stable organic biradicals. The spectral dispersion of Verdet constant, which quantifies magneto-optic response, differs substantially between the base polymer and the nanocomposite. We employed a microscopic model, supported by atomistic calculations, to rationalize the behavior of this nanocomposite system. The suggested mechanism involves magnetic coupling between helical conjugated polymer fibrils, with spatially delocalized helical π-electron density, and the high density of spin states provided by the biradical dopants, which leads to synergistic enhancement of magneto-optic response. Our combined experimental and theoretical studies reveal that the manipulation of magnetic coupling in this new class of magneto-optic materials offers an opportunity to tailor the magnitude, sign, and spectral dispersion of the Verdet constant over a broad range of wavelengths, from the UV to the near-IR. This provides a new strategy for creating conformable materials with extraordinary magneto-optic activity, which can ultimately enable new applications requiring spatially and temporally resolved measurement of extremely weak magnetic fields. In particular, magneto-optic materials, presently employed in technologies like optical isolators and optical circulators, could be used in ultrasensitive optical magnetometers. This, in turn, could open a path toward mapping of brain activity via optical magnetoencephalography.

Modulated spin helicity stabilized by incommensurate orbital density waves in a quadruple perovskite manganite

Through a combination of neutron diffraction and Landau theory we describe the spin ordering in the ground state of the quadruple perovskite manganite ${\mathrm{CaMn}}_{7}{\mathrm{O}}_{12}$---a magnetic multiferroic supporting an incommensurate orbital density wave that onsets above the magnetic ordering temperature, ${T}_{\mathrm{N}1}=90$ K. The multi-$\mathbf{k}$ magnetic structure in the ground state was found to be a nearly-constant-moment helix with modulated spin helicity, which oscillates in phase with the orbital occupancies on the ${\mathrm{Mn}}^{3+}$ sites via trilinear magneto-orbital coupling. Our phenomenological model also shows that, above ${T}_{\mathrm{N}2}=48$ K, the primary magnetic order parameter is locked into the orbital wave by an admixture of helical and collinear spin density wave structures. Furthermore, our model naturally explains the lack of a sharp dielectric anomaly at ${T}_{\mathrm{N}1}$ and the unusual temperature dependence of the electrical polarization.

A 3-D MHD equilibrium description of nonlinearly saturated ideal external kink/peeling structures in tokamaks

Novel free boundary magnetohydrodynamic equilibrium states with spontaneous three-dimensional (3-D) deformations of the plasma–vacuum interface are computed. The structures obtained look like saturated ideal external kink/peeling modes. Large edge pressure gradients yield toroidal mode number $n=1$ distortions when the edge bootstrap current is large and higher $n$ corrugations when this current is small. Linear ideal MHD stability analyses confirm the nonlinear saturated ideal kink equilibrium states produced and we can identify the Pfirsch–Schlüter current as the main linear instability driving mechanism when the edge pressure gradient is large. The dominant non-axisymmetric component of this Pfirsch–Schlüter current drives a near resonant helical parallel current density ribbon that aligns with the near vanishing magnetic shear region caused by the edge bootstrap current. This current ribbon is a manifestation of the outer mode previously found on JET (Solano 2010). We claim that the equilibrium corrugations describe structures that are commonly observed in quiescent H-mode tokamak discharges.

Dense Helical Electron Bunch Generation in Near-Critical Density Plasmas with Ultrarelativistic Laser Intensities.

The mechanism for emergence of helical electron bunch(HEB) from an ultrarelativistic circularly polarized laser pulse propagating in near-critical density(NCD) plasma is investigated. Self-consistent three-dimensional(3D) Particle-in-Cell(PIC) simulations are performed to model all aspects of the laser plasma interaction including laser pulse evolution, electron and ion motions. At a laser intensity of 1022 W/cm2, the accelerated electrons have a broadband spectrum ranging from 300 MeV to 1.3 GeV, with the charge of 22 nano-Coulombs(nC) within a solid-angle of 0.14 Sr. Based on the simulation results, a phase-space dynamics model is developed to explain the helical density structure and the broadband energy spectrum.

Transformation of flow structure on a rotating wing due to variation of radius of gyration

The flow structure on a rotating wing (rectangular plate) is characterized over a range of travel distance at different radii of gyration. Travel distance is defined as the length of the arc subtended by the radius of gyration. Stereoscopic particle image velocimetry is employed to determine the volumetric flow structure, in the form of three-dimensional surfaces of the q-criterion, helical density, and downwash velocity. These representations are complemented by sectional patterns of vorticity and tangential velocity. An increase in the radius of gyration reduces the influence of rotation on the flow structure. At small radius of gyration, a coherent leading-edge vortex develops rapidly and then persists over a range of travel distance. At moderate radius of gyration, this leading-edge vortex is replaced by an arch vortex, which develops relatively slowly over a larger travel distance, and is eventually swept into the wake of the wing. The foregoing classes of vortical structures are associated with distinctive patterns of: helical density, which represents the axial vorticity flux through the three-dimensional vortex system; downwash related to the strengths of the components of the vortex system; and tangential velocity associated with the extent of reverse flow, or stall.

Magnetic order on a topological insulator surface with warping and proximity-induced superconductivity

We determine the nature of the magnetic order on the surface of a topological insulator (TI) which develops due to hexagonal warping and the resulting Fermi surface (FS) nesting in the presence of a repulsive Hubbard interaction. For this purpose we investigate the spin susceptibility and derive a Landau theory to compare the different accessible phases. For a nearly hexagonal FS and sufficiently strong interaction the magnetic ground state is formed by a skyrmion lattice, i.e., by a superposition of three helical spin density waves which preserves C$_3$ symmetry. The magnetic ground state is topologically nontrivial with a nonzero skyrmion charge, which can be stabilized and controlled by an applied magnetic field. By bringing the TI in proximity to a conventional superconductor one can engineer a C$_3$-symmetric topological superconductor. We explore the modification of the phase diagram as well as the mutual influence between the skyrmion structure and a multipolar distribution of supercurrents, which can provide information about the underlying skyrmion charge.

Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease.

Recent large-scale genome-wide association studies have discovered several genetic variants associated with Alzheimer disease (AD); however, the extent to which DNA methylation in these AD loci contributes to the disease susceptibility remains unknown. To examine the association of brain DNA methylation in 28 reported AD loci with AD pathologies. Ongoing community-based clinical pathological cohort studies of aging and dementia (the Religious Orders Study and the Rush Memory and Aging Project) among 740 autopsied participants 66.0 to 108.3 years old. DNA methylation levels at individual CpG sites generated from dorsolateral prefrontal cortex tissue using a bead assay. Pathological diagnosis of AD by National Institute on Aging-Reagan criteria following a standard postmortem examination. Overall, 447 participants (60.4%) met the criteria for pathological diagnosis of AD. Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 was associated with pathological AD. The association was robustly retained after replacing the binary trait of pathological AD with 2 quantitative and molecular specific hallmarks of AD, namely, Aβ load and paired helical filament tau tangle density. Furthermore, RNA expression of transcripts of SORL1 and ABCA7 was associated with paired helical filament tau tangle density, and the expression of BIN1 was associated with Aβ load. Brain DNA methylation in multiple AD loci is associated with AD pathologies. The results provide further evidence that disruption of DNA methylation is involved in the pathological process of AD.

On the formation of m = 1, n = 1 density snakes

The m/n = 1/1 helical ion density “snake” located near the q = 1 magnetic surface in a toroidal, magnetically confined plasma arises naturally in resistive MHD, when the plasma density evolves separately from pressure. Nonlinear numerical simulations show that a helical density perturbation applied around q = 1 can form a quasi-steady state over q≳1 with T̃ of opposite average sign to ñ. Two principal outcomes depend on the magnitude of ñ/n and the underlying stability of the 1/1 internal kink mode. For a small q<1 central region, a moderate helical density drives a new, slowly growing type of nonlinear 1/1 internal kink inside q<1, with small ñ and ∇p̃≃∇(nT̃). The hot kink core moves away from, or perpendicular to, the high density region near q≃1, preserving the snake density during a sawtooth crash. The mode resembles the early stage of heavy-impurity-ion snakes in ohmic discharges, including recent observations in Alcator C-Mod. For a larger, more unstable q<1 region, the helical density perturbation drives a conventional 1/1 kink where ñ aligns with T̃, leading to a rapid sawtooth crash. The crash redistributes the density to a localized helical concentration inside q≲1, similar to experimentally observed snakes that are initiated by a sawtooth crash.

Experimental observation of helical microbunching of a relativistic electron beam

Experimental observation of the microbunching of a relativistic electron beam at the second harmonic interaction frequency of a helical undulator is presented. The microbunching signal is observed from the coherent transition radiation of the electron beam and indicates experimental evidence of a dominantly helical electron beam density distribution. This result is in agreement with theoretical and numerical predictions and provides a proof-of-principle demonstration of proposed schemes designed to generate light with orbital angular momentum in high-gain free-electron lasers.

Incommensurate spin order in the metallic perovskite MnVO3

Incommensurate Mn spin order has been discovered in the perovskite MnVO${}_{3}$ containing localized 3d${}^{5}$ Mn${}^{2+}$ and itinerant 3d${}^{1}$ V${}^{4+}$ states. This phase has a distorted Pnma crystal structure (a = 5.2741(6) \AA{}, b = 7.4100(11) \AA{}, and c = 5.1184(8) \AA{} at 300 K) and is metallic at temperatures of 2--300 K and at pressures of up to 67 kbar. Neutron scattering reveals a (0.29 0 0) magnetic vector below the 46 K spin ordering transition, and both helical and spin density wave orderings are consistent with the diffraction intensities. Electronic structure calculations show large exchange splittings of the Mn and V 3d bands, and (${k}_{x}$ 0 0) crossings of the Fermi energy by spin up and down V 3d bands may give rise to Ruderman-Kittel-Kasuya-Yosida coupling of Mn moments, in addition to their superexchange interactions.

A unified convention for biological assemblies with helical symmetry.

Assemblies with helical symmetry can be conveniently formulated in many distinct ways. Here, a new convention is presented which unifies the two most commonly used helical systems for generating helical assemblies from asymmetric units determined by X-ray fibre diffraction and EM imaging. A helical assembly is viewed as being composed of identical repetitive units in a one- or two-dimensional lattice, named 1-D and 2-D helical systems, respectively. The unification suggests that a new helical description with only four parameters [n(1), n(2), twist, rise], which is called the augmented 1-D helical system, can generate the complete set of helical arrangements, including coverage of helical discontinuities (seams). A unified four-parameter characterization implies similar parameters for similar assemblies, can eliminate errors in reproducing structures of helical assemblies and facilitates the generation of polymorphic ensembles from helical atomic models or EM density maps. Further, guidelines are provided for such a unique description that reflects the structural signature of an assembly, as well as rules for manipulating the helical symmetry presentation.

A fluid solver based on vorticity–helical density equations with application to a natural convection in a cubic cavity

SUMMARYWe study numerically a recently introduced formulation of incompressible Newtonian fluid equations in vorticity–helical density and velocity–Bernoulli pressure variables. Unlike most numerical methods based on vorticity equations, the current approach provides discrete solutions with mass conservation, divergence‐free vorticity, and accurate kinetic energy balance in a simple and natural way. The method is applied to compute buoyancy‐driven flows in a differentially heated cubic enclosure in the Boussinesq approximation for Ra ∈ {104,105,106}. The numerical solutions on a finer grid are of benchmark quality. The computed helical density allows quantification of the three‐dimensional nature of the flow. Copyright © 2011 John Wiley & Sons, Ltd.

Cholesteric order in systems of helical Yukawa rods

We consider the interaction potential between two chiral rod-like colloids which consist of athin cylindrical backbone decorated with a helical charge distribution on the cylindersurface. For sufficiently slender helical rods a simple scaling expression is derived whichrelates the chiral ‘twisting’ potential to the microscopic properties of the particles, such asthe internal helical pitch, charge density and electrostatic screening parameter. To predictthe behaviour of the macroscopic cholesteric pitch of the fluid bulk phase we invoke asimple second-virial theory generalized to treat anisotropic states with weakly twisteddirector fields. It is shown that, while particles with weakly coiled helices always form acholesteric phase whose helical sense is commensurate with that of the internalhelix, more strongly coiled rods lead to the formation of a cholesteric state ofopposite sense. The correlation between the helical symmetry at the microscopic andmacroscopic scale is found to be very sensitive to the pitch of the Yukawa helix. Mixinghelical particles of sufficiently disparate length and internal pitch may give rise toa demixing of the uniform cholesteric phase into two fractions with a differentmacroscopic pitch. Our findings could be relevant to the interpretation of experimentalobservations in systems of cellulose and chitin microfibres, DNA and fd virus rods.

Anisotropic surface transport in topological insulators in proximity to a helical spin density wave

We study the effects of spatially localized breakdown of time reversal symmetry on the surface of a topological insulator (TI) due to proximity to a helical spin density wave (HSDW). The HSDW acts like an externally applied one-dimensional periodic (magnetic) potential for spins on the surface of the TI, rendering the Dirac cone on the TI surface highly anisotropic. The decrease in group velocity along the direction $\mathrm{x\ifmmode \hat{}\else \^{}\fi{}}$ of the applied spin potential is twice as great as that perpendicular to $\mathrm{x\ifmmode \hat{}\else \^{}\fi{}}$. At the Brillouin zone boundaries, it also gives rise to new semi-Dirac points that have a linear dispersion along $\mathrm{x\ifmmode \hat{}\else \^{}\fi{}}$ but a quadratic dispersion perpendicular to $\mathrm{x\ifmmode \hat{}\else \^{}\fi{}}$. The group velocity of electrons at these new semi-Dirac points is also shown to be highly anisotropic. Experiments using TI systems on multiferroic substrates should realize our predictions. We further discuss the effects of other forms of spin density waves on the surface transport property of TIs.

The Crystal Structure of Dynein Intermediate Chain-Light Chain Roadblock Complex Gives New Insights into Dynein Assembly

The roadblock/LC7 dynein light chain is a ubiquitous component of all dyneins and is essential for many diverse processes including proper axonal transport and dendrite growth. In addition, LC7 functions in non-dynein transcriptional activation of the transforming growth factor-beta complex. Crystal structures of Drosophila melanogaster LC7 in the apo form and in complex with a segment of the disordered N-terminal domain of dynein intermediate chain (IC) provide the first definitive identification of the IC sequence recognized by LC7. The site, confirmed by isothermal titration calorimetry studies, overlaps the IC sequence considered in the literature to be an IC self-association domain. The IC peptide binds as two amphipathic helices that lie along an extensive hydrophobic cleft on LC7 and ends with a polar side-chain interaction network that includes conserved residues from both proteins. The LC7 recognition sequence on IC and its interface with LC7 are well conserved and are, thus, likely representative of all IC x LC7 structures. Interestingly, the position of bound IC in the IC x LC7 complex mimics a helix that is integrated into the primary structure in distantly related LC7 homologs. The IC x LC7 structure further shows that the naturally occurring robl(Z) deletion mutation contains the majority of the IC binding site and suggests that promotion of IC binding by phosphorylation of LC7 is an indirect effect.

Velocity–vorticity–helicity formulation and a solver for the Navier–Stokes equations

For the three-dimensional incompressible Navier–Stokes equations, we present a formulation featuring velocity, vorticity and helical density as independent variables. We find the helical density can be observed as a Lagrange multiplier corresponding to the divergence-free constraint on the vorticity variable, similar to the pressure in the case of the incompressibility condition for velocity. As one possible practical application of this new formulation, we consider a time-splitting numerical scheme based on an alternating procedure between vorticity–helical density and velocity–Bernoulli pressure systems of equations. Results of numerical experiments include a comparison with some well-known schemes based on pressure–velocity formulation and illustrate the competitiveness on the new scheme as well as the soundness of the new formulation.