Motion Of Defects Research Articles

IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux

Huntington's disease (HD), an inherited neurodegenerative disorder, is caused by an expansion of cytosine-adenine-guanine repeats in the huntingtin gene. The aggregation of mutant huntingtin (mtHTT) and striatal cell loss are representative features to cause uncontrolled movement and cognitive defect in HD. However, underlying mechanism of mtHTT aggregation and cell toxicity remains still elusive. Here, to find new genes modulating mtHTT aggregation, we performed cell-based functional screening using the cDNA expression library and isolated IRE1 gene, one of endoplasmic reticulum (ER) stress sensors. Ectopic expression of IRE1 led to its self-activation and accumulated detergent-resistant mtHTT aggregates. Treatment of neuronal cells with ER stress insults, tunicamycin and thapsigargin, increased mtHTT aggregation via IRE1 activation. The kinase activity of IRE1, but not the endoribonuclease activity, was necessary to stimulate mtHTT aggregation and increased death of neuronal cells, including SH-SY5Y and STHdhQ111/111 huntingtin knock-in striatal cells. Interestingly, ER stress impaired autophagy flux via IRE1-TRAF2 pathway, thus enhancing cellular accumulation of mtHTT. Atg5 deficiency in M5-7 cells increased mtHTT aggregation but blocked ER stress-induced mtHTT aggregation. Further, ER stress markers including p-IRE1 and autophagy markers such as p62 were up-regulated exclusively in the striatal tissues of HD mouse models and in HD patients. Moreover, down-regulation of IRE1 expression rescues the rough-eye phenotype by mtHTT in a HD fly model. These results suggest that IRE1 plays an essential role in ER stress-mediated aggregation of mtHTT via the inhibition of autophagy flux and thus neuronal toxicity of mtHTT aggregates in HD.

Polarization switching and relaxation dynamics of bismuth layered ferroelectric thin films: Role of oxygen defect sites and crystallinity

Influence of oxygen vacancies and crystallinity on polarization switching and relaxation dynamics of Bi${}_{3.15}$Nd${}_{0.85}$Ti${}_{3}$O${}_{12}$ (BNT) thin films on Pt electrodes have been studied by piezoresponse force microscopy (PFM). Heat treatment of the study induced oxygen vacancies in Bi${}_{2}$O${}_{2}$${}^{+2}$ layers not in TiO${}_{6}$${}^{\ensuremath{-}8}$ octahedra and changes in crystallinity of the films. Oxygen atoms have two different locations unique in the bismuth layered ferroelectrics and, in particular, the oxygen vacancies at the Bi${}_{2}$O${}_{2}$${}^{+2}$ layers turned out to be critical for retention of polarization states. Perfect crystallinity in the arrangement of atoms through $c$-axis is surprisingly found to sustain polarization switching. Electrodynamics of the bound charges in the films with oxygen deficiency and imperfectness of crystallinity are presented in a dynamic model with random-walk motion of point defects and a diffusive migration of mobile and bound charges and their clusters. For the stretched exponential decay of the bound charges in the films, the scaling exponents are 0.086 and 0.289 for well crystalline-thin films.

An elasto-plastic theory of dislocation and disclination fields

A linear theory of the elasto-plasticity of crystalline solids based on a continuous representation of crystal defects – dislocations and disclinations – is presented. The model accounts for the translational and rotational aspects of lattice incompatibility, respectively associated with the presence of dislocations and disclinations. The defects content relates to the incompatible plastic strain and curvature tensors. The stress state is described by using the conjugate variables to strain and curvature, i.e., the stress and couple-stress tensors. Defect motion is described by two transport equations. A dynamic interplay between dislocations and disclinations results from a disclination-induced source term in the transport of dislocations. Thermodynamic guidance provides the driving forces conjugate to dislocation and disclination velocity in a continuous context, as well as admissible constitutive relations for the latter. When dislocation and disclination velocity vanish, the model reduces to deWit’s elasto-static theory of crystal defects. It also reduces to Acharya’s linear elasto-plastic theory for dislocation fields when the disclination density is ignored. The theory is intended for use in instances where rotational defects matter, such as grain boundaries. To illustrate its applicability, a finite high-angle tilt boundary is modeled using a disclination dipole and its behavior under tensile loading normal to the boundary is shown.

D-foam-induced flavor condensates and breaking of supersymmetry in free Wess-Zumino fluids

Recently we argued that a particular model of string-inspired quantum space-time foam (D-foam) may induce oscillations and mixing among flavoured particles. As a result, rather than the mass-eigenstate vacuum, the correct ground state to describe the underlying dynamics is the flavour vacuum, proposed some time ago by Blasone and Vitiello as a description of quantum field theories with mixing. At the microscopic level, the breaking of target-space supersymmetry is induced in our space-time foam model by the relative transverse motion of brane defects. Motivated by these results, we show that the flavour vacuum, introduced through an inequivalent representation of the canonical (anti-) commutation relations, provides a vehicle for the breaking of supersymmetry (SUSY) at a low-energy effective field theory level; on considering the flavour-vacuum expectation value of the energy-momentum tensor and comparing with the form of a perfect relativistic fluid, it is found that the bosonic sector contributes as dark energy while the fermion contribution is like dust. This indicates a strong and novel breaking of SUSY, of a non-perturbative nature, which may characterize the low energy field theory of certain quantum gravity models.

Specific roles for the GATA transcription factors end-1 and end-3 during C. elegans E-lineage development

end-1 and end-3 are GATA transcription factors important for specifying endoderm cell fate in Caenorhabditis elegans. Deletion of both factors together results in larval arrest, 0% survival and a fate change in the endoderm-specifying E lineage. Individual deletions of either factor, however, result in the development of viable, fertile adults, with 100% of worms developing to adults for end-1(−) and 95% for end-3(−). We sought to quantify the variable phenotypes seen in both deletions using automated cell lineaging. We quantified defects in cell lifetime, cell movement and division axis in end-3(−) embryos, while quantifying perturbations in downstream reporter gene expression in strains with homozygous deletions for either gene, showing that each deletion leads to a unique profile of downstream perturbations in gene expression and cellular phenotypes with a high correlation between early and late defects. Combining observations in both cellular and gene expression defects we found that misaligned divisions at the E2 stage resulted in ectopic expression of the Notch target ref-1 in end-3(−) embryos. Using a maximum likelihood phylogenetic approach we found end-1 and end-3 split to form two distinct clades within the Caenorhabditis lineage with distinct DNA-binding structures. These results indicate that end-1 and end-3 have each evolved into genes with unique functions during endoderm development, that end-3(−) embryos have a delay in the onset of E lineage cell fate and that end-1 has only a partially penetrant ability to activate E lineage fate.

Experimental analysis of the fatigue of shape memory alloys through power-law statistics

In this paper, fatigue failure is investigated by studying the collective motion of defects inside a NiTi shape memory alloys material. To this end, an experimental study of the statistical distributions of acoustic emissions avalanches due to these defects along cycling is presented. It is found that these distributions follow power-law statistics for which the evolutions of exponents through cyclic driving are estimated. The goal is to track changes in the dissipation modes through the shifts of the power-law exponents and consequently identify fatigue failure precursors. It’s shown that these fatigue precursors can be interpreted using the paradigm of self organized criticality (SOC).

Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores

Aurora B (AurB) is a mitotic kinase responsible for multiple aspects of mitotic progression, including assembly of the outer kinetochore. Cytoplasmic dynein is an abundant kinetochore protein whose recruitment to kinetochores requires phosphorylation. To assess whether AurB regulates recruitment of dynein to kinetochores, we inhibited AurB using ZM447439 or a kinase-dead AurB construct. Inhibition of AurB reduced accumulation of dynein at kinetochores substantially; however, this reflected a loss of dynein-associated proteins rather than a defect in dynein phosphorylation. We determined that AurB inhibition affected recruitment of the ROD, ZW10, zwilch (RZZ) complex to kinetochores but not zwint-1 or more-proximal kinetochore proteins. AurB phosphorylated zwint-1 but not ZW10 in vitro, and three novel phosphorylation sites were identified by tandem mass spectrometry analysis. Expression of a triple-Ala zwint-1 mutant blocked kinetochore assembly of RZZ-dependent proteins and induced defects in chromosome movement during prometaphase. Expression of a triple-Glu zwint-1 mutant rendered cells resistant to AurB inhibition during prometaphase. However, cells expressing the triple-Glu mutant failed to satisfy the spindle assembly checkpoint (SAC) at metaphase because poleward streaming of dynein/dynactin/RZZ was inhibited. These studies identify zwint-1 as a novel AurB substrate required for kinetochore assembly and for proper SAC silencing at metaphase.

Diffusion in Coulomb crystals

Diffusion in Coulomb crystals can be important for the structure of neutron star crusts. We determine diffusion constants D from molecular dynamics simulations. We find that D for Coulomb crystals with relatively soft-core 1/r interactions may be larger than D for Lennard-Jones or other solids with harder-core interactions. Diffusion, for simulations of nearly perfect body-centered-cubic lattices, involves the exchange of ions in ringlike configurations. Here ions "hop" in unison without the formation of long lived vacancies. Diffusion, for imperfect crystals, involves the motion of defects. Finally, we find that diffusion, for an amorphous system rapidly quenched from Coulomb parameter Γ=175 to Coulomb parameters up to Γ=1750, is fast enough that the system starts to crystalize during long simulation runs. These results strongly suggest that Coulomb solids in cold white dwarf stars, and the crust of neutron stars, will be crystalline and not amorphous.

Creation of microcracks in porcelain during firing

Quartz porcelain samples were tested by acoustic emission (AE) and sonic resonant methods (sensitive to nucleation and motion of structural defects) during a cooling stage of the firing process from temperature of 1250 °C. As a consequence of the mismatch of thermal expansion coefficients of the glass and the mullite phases, and the quartz particles, microcracking begun at the temperature of the glass transition (∼800 °C) and continued in several stages until the temperature reached 300 °C. A non-monotonous behaviour of the Young's modulus and temporary vanishing of the AE signals on cooling between 573 and 500 °C confirm the significance of the β → α transition, which lies mainly upon the reversal of thermal stresses acting on the glass matrix and the quartz particles. Consequently, above this temperature, radial cracks nucleating at the quartz particles appear, whereas below this temperature, circumferential cracks around the particles are produced.

Elemental redistribution in a nanocrystalline Ni–Fe alloy induced by high-pressure torsion

• Elemental distribution of a nc Ni–Fe alloy before and after high-pressure torsion. • The supersaturated Ni–Fe solid solution was stable under HPT. • C and S atoms further segregated to the remaining GBs during grain growth. • GB diffusion and the motion of defects facilitate the elemental redistribution. An electrochemically deposited nanocrystalline supersaturated face-centred-cubic Ni–21 at.% Fe alloy with an initial average grain size of ∼21 nm was processed using high-pressure torsion (HPT) that resulted in grain growth via grain rotation and coalescence to an average grain size of ∼53 nm. Atom probe tomography investigations revealed that the supersaturated Ni–Fe solid solution was stable under HPT and that C and S atoms, which are the major impurities in the material and segregated to the grain boundaries (GBs) of the as-deposited material, migrated from disappearing GBs to the remaining GBs during HPT. We propose that the elemental redistribution was facilitated by GB diffusion and the motion of a large volume of HPT-induced defects at the GB regions during the grain growth process. This elemental redistribution process is different from other HPT-induced elemental redistribution processes reported in the literature.

Metadislocations in the complex metallic alloys T–Al–Mn– (Pd, Fe)

We investigate dislocations in the complex metallic alloys T–Al–Mn–Pd and T–Al–Mn–Fe using high-resolution aberration-corrected scanning transmission electron microscopy. The dislocations consist of a large core and separated escort defects [1]. Upon movement, dislocations and escort defects locally transform the material and introduce stacks of planar faults which represent a slab of a different but related structure. Deformation modes involving glide and climb are observed. We find different types of dislocations with Burgers vectors b → = - ( - τ ) - n ( 0 0 1 ) , with n = 2, 3, 4. They are associated to two, four and six planar faults, respectively, and are identified as metadislocations. The structural connection between metadislocations in the present phase and those in R-, ε 6-, and ξ-phases is discussed.

The zebrafish maternal-effect gene mission impossible encodes the DEAH-box helicase Dhx16 and is essential for the expression of downstream endodermal genes

Early animal embryonic development requires maternal products that drive developmental processes prior to the activation of the zygotic genome at the mid-blastula transition. During and after this transition, maternal products may continue to act within incipient zygotic developmental programs. Mechanisms that control maternally-inherited products to spatially and temporally restrict developmental responses remain poorly understood, but necessarily depend on posttranscriptional regulation. We report the functional analysis and molecular identification of the zebrafish maternal-effect gene mission impossible (mis). Our studies suggest requirements for maternally-derived mis function in events that occur during gastrulation, including cell movement and the activation of some endodermal target genes. Cell transplantation experiments show that the cell movement defect is cell autonomous. Within the endoderm induction pathway, mis is not required for the activation of early zygotic genes, but is essential to implement nodal activity downstream of casanova/sox 32 but upstream of sox17 expression. Activation of nodal signaling in blastoderm explants shows that the requirement for mis function in endoderm gene induction is independent of the underlying yolk cell. Positional cloning of mis, including genetic rescue and complementation analysis, shows that it encodes the DEAH-box RNA helicase Dhx16, shown in other systems to act in RNA regulatory processes such as splicing and translational control. Analysis of a previously identified insertional dhx16 mutation shows that the zygotic component of this gene is also essential for embryonic viability. Our studies provide a striking example of the interweaving of maternal and zygotic genetic functions during the egg-to-embryo transition. Maternal RNA helicases have long been known to be involved in the development of the animal germ line, but our findings add to growing evidence that these factors may also control specific gene expression programs in somatic tissues.

Defective motion processing in children with cerebral visual impairment due to periventricular white matter damage

We sought to characterize visual motion processing in children with cerebral visual impairment (CVI) due to periventricular white matter damage caused by either hydrocephalus (eight individuals) or periventricular leukomalacia (PVL) associated with prematurity (11 individuals). Using steady-state visually evoked potentials (ssVEP), we measured cortical activity related to motion processing for two distinct types of visual stimuli: 'local' motion patterns thought to activate mainly primary visual cortex (V1), and 'global' or coherent patterns thought to activate higher cortical visual association areas (V3, V5, etc.). We studied three groups of children: (1) 19 children with CVI (mean age 9y 6mo [SD 3y 8mo]; 9 male; 10 female); (2) 40 neurologically and visually normal comparison children (mean age 9y 6mo [SD 3y 1mo]; 18 male; 22 female); and (3) because strabismus and amblyopia are common in children with CVI, a group of 41 children without neurological problems who had visual deficits due to amblyopia and/or strabismus (mean age 7y 8mo [SD 2y 8mo]; 28 male; 13 female). We found that the processing of global as opposed to local motion was preferentially impaired in individuals with CVI, especially for slower target velocities (p=0.028). Motion processing is impaired in children with CVI. ssVEP may provide useful and objective information about the development of higher visual function in children at risk for CVI.

A perturbative approach to the backflow dynamics of nematic defects

We present an asymptotic theory that includes in a perturbative expansion the coupling effects between the director dynamics and the velocity field in a nematic liquid crystal. Backflow effects are most significant in the presence of defect motion, since in this case the presence of a velocity field may strongly reduce the total energy dissipation and thus increase the defect velocity. As an example, we illustrate how backflow influences the speeds of opposite-charged defects.

Impact of defect creation and motion on the thermodynamics and large-scale reorganization of self-assembled clathrin lattices

We develop a theoretical model for the thermodynamics and kinetics of clathrin self-assembly. Our model addresses the behavior in two dimensions and can be easily extended to three dimensions, facilitating the study of membrane, surface, and bulk assembly. The clathrin triskelia are modeled as flexible pinwheels that form leg-leg associations and resist bending and stretching deformations. Thus, the pinwheels are capable of forming a range of ring structures, including 5-, 6-, and 7-member rings that are observed experimentally. Our theoretical model employs Brownian dynamics to track the motion of clathrin pinwheels at sufficiently long time scales to achieve complete assembly. Invoking theories of dislocation-mediated melting in two dimensions, we discuss the phase behavior for clathrin self-assembly as predicted by our theoretical model. We demonstrate that the generation of 5–7 defects in an otherwise perfect honeycomb lattice resembles creation of two dislocations with equal and opposite Burgers vectors. We use orientational- and translational-order correlation functions to predict the crystalline-hexatic and hexatic-liquid phase transitions in clathrin lattices. These results illustrate the pivotal role that molecular elasticity plays in the physical behavior of self-assembling and self-healing materials.

Universal quantum computation in a semiconductor quantum wire network

Universal quantum computation (UQC) using Majorana fermions on a 2D topological superconducting (TS) medium remains an outstanding open problem. This is because the quantum gate set that can be generated by braiding of the Majorana fermions does not include \emph{any} two-qubit gate and also the single-qubit $\pi/8$ phase gate. In principle, it is possible to create these crucial extra gates using quantum interference of Majorana fermion currents. However, it is not clear if the motion of the various order parameter defects (vortices, domain walls, \emph{etc.}), to which the Majorana fermions are bound in a TS medium, can be quantum coherent. We show that these obstacles can be overcome using a semiconductor quantum wire network in the vicinity of an $s$-wave superconductor, by constructing topologically protected two-qubit gates and any arbitrary single-qubit phase gate in a topologically unprotected manner, which can be error corrected using magic state distillation. Thus our strategy, using a judicious combination of topologically protected and unprotected gate operations, realizes UQC on a quantum wire network with a remarkably high error threshold of $0.14$ as compared to $10^{-3}$ to $10^{-4}$ in ordinary unprotected quantum computation.

Nonlinear theory of waves in solid state with cardinally changing crystalline structure

A nonlinear theory of propagating periodic and nonlinear solitary waves (like kinks and solitons) related to the motion of defects in crystals and of specific periodic waves into which the former ones transform in the field of the compression stress was developed. The role of intense tension stress leading to the heavy structural rearrangement of the crystal as a result of the effect of the external stress on the interatomic potential barriers was taken into account as well. Crystals with a complex lattice consisting of two sublattices were considered. Arbitrarily large displacements of sublattices were analyzed. The nonlinear theory is based on an additional element of the translational symmetry typical for complex lattices but not introduced earlier in solid-state physics. The variational equations of macroscopic and microscopic displacements turn out to be a nonlinear generalization of the linear equations of acoustic and optical modes obtained by Carman, Born, and Huang Kun. The microscopic displacement fields are described by the nonlinear sine-Gordon equation. In the one-dimensional case, exact solutions of the nonlinear equations were found and their features were revealed. In the case of two-dimensional (2+1) fields, new methods of the exact solutions of the sine-Gordon equation were developed. They describe the interaction of the nonlinear waves with the structural inhomogeneities of solid state due to the external fields of stress and deformations.

The cell adhesion-associated protein Git2 regulates morphogenetic movements during zebrafish embryonic development

Signaling through cell adhesion complexes plays a critical role in coordinating cytoskeletal remodeling necessary for efficient cell migration. During embryonic development, normal morphogenesis depends on a series of concerted cell movements; but the roles of cell adhesion signaling during these movements are poorly understood. The transparent zebrafish embryo provides an excellent system to study cell migration during development. Here, we have identified zebrafish git2a and git2b, two new members of the GIT family of genes that encode ArfGAP proteins associated with cell adhesions. Loss-of-function studies revealed an essential role for Git2a in zebrafish cell movements during gastrulation. Time-lapse microscopy analysis demonstrated that antisense depletion of Git2a greatly reduced or arrested cell migration towards the vegetal pole of the embryo. These defects were rescued by expression of chicken GIT2, indicating a specific and conserved role for Git2 in controlling embryonic cell movements. Git2a knockdown embryos showed defects in cell morphology that were associated with reduced cell contractility. We show that Git2a is required for phosphorylation of myosin light chain (MLC), which regulates myosin II-mediated cell contractility. Consistent with this, embryos treated with Blebbistatin-a small molecule inhibitor for myosin II activity-exhibited cell movement defects similar to git2a knockdown embryos. These observations provide in vivo evidence of a physiologic role for Git2a in regulating cell morphogenesis and directed cell migration via myosin II activation during zebrafish embryonic development.

Elastic scattering studies of aligned DMPC multilayers on different hydrations 1

Biological membranes, consisting mainly of phospholipids and proteins, are organized in a bilayered structure which exhibits dynamical behaviour within time regimes ranging from 10–12 s with the motion of alkyl chain defects and 1 s corresponding to collective excitations of the bilayer [Europhysics Letters 8 (1989), 201–206]. With the prominent role hydration plays on the structural phase behaviour of phospholipids membranes, it is essential for a better description of membranes to understand also the influence of hydration on the dynamics of membrane systems. In the present study we have performed neutron scattering investigations on highly oriented DMPC-d54 multilayers at two different relative humidity (rh) levels. Our results reveal the strong influence of hydration on the local membrane dynamics, i.e., head group dynamics.

Rotational Solid Friction of a Nematic Liquid Crystal

Liquid crystal defects are used as probes to study the local reorientation dynamics of the nematic surface director on SiO(x) alignment layers. The tracking of the defect's motion reveals the presence of solid friction forces, unexpected in this complex viscous fluid. We identify the director pinning due to a surface quenched disorder as a possible mechanism that gives rise to the measured solid friction.