167 research outputs found
Nucleotide– and Mal3-dependent changes in fission yeast microtubules suggest a structural plasticity view of dynamics
Using cryo-electron microscopy, we characterize the architecture of microtubules assembled from Schizosaccharomyces pombe tubulin, in the presence and absence of their regulatory partner Mal3. Cryo-electron tomography reveals that microtubules assembled from S. pombe tubulin have predominantly B-lattice interprotofilament contacts, with protofilaments skewed around the microtubule axis. Copolymerization with Mal3 favors 13 protofilament microtubules with reduced protofilament skew, indicating that Mal3 adjusts interprotofilament interfaces. A 4.6-Å resolution structure of microtubule-bound Mal3 shows that Mal3 makes a distinctive footprint on the S. pombe microtubule lattice and that unlike mammalian microtubules, S. pombe microtubules do not show the longitudinal lattice compaction associated with EB protein binding and GTP hydrolysis. Our results firmly support a structural plasticity view of microtubule dynamics in which microtubule lattice conformation is sensitive to a variety of effectors and differently so for different tubulins
Kinetics of Ordering in Fluctuation-Driven First-Order Transitions: Simulations and Dynamical Renormalization
Many systems where interactions compete with each other or with constraints
are well described by a model first introduced by Brazovskii. Such systems
include block copolymers, alloys with modulated phases, Rayleigh-Benard Cells
and type-I superconductors. The hallmark of this model is that the fluctuation
spectrum is isotropic and has a minimum at a nonzero wave vector represented by
the surface of a d-dimensional hyper-sphere. It was shown by Brazovskii that
the fluctuations change the free energy structure from a to a
form with the disordered state metastable for all quench depths.
The transition from the disordered to the periodic, lamellar structure changes
from second order to first order and suggests that the dynamics is governed by
nucleation. Using numerical simulations we have confirmed that the equilibrium
free energy function is indeed of a form. A study of the dynamics,
however, shows that, following a deep quench, the dynamics is described by
unstable growth rather than nucleation. A dynamical calculation, based on a
generalization of the Brazovskii calculations shows that the disordered state
can remain unstable for a long time following the quench.Comment: 18 pages, 15 figures submitted to PR
Ordering of the lamellar phase under a shear flow
The dynamics of a system quenched into a state with lamellar order and
subject to an uniform shear flow is solved in the large-N limit. The
description is based on the Brazovskii free-energy and the evolution follows a
convection-diffusion equation. Lamellae order preferentially with the normal
along the vorticity direction. Typical lengths grow as (with
logarithmic corrections) in the flow direction and logarithmically in the shear
direction. Dynamical scaling holds in the two-dimensional case while it is
violated in D=3
SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture
Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell populations that had been selected for TRAIL-resistance from initially TRAIL-sensitive populations. SAHA may increase TRAIL sensitivity in insensitive cells, but not in cells that have specifically been selected for acquired TRAIL-resistance. [Abstract copyright: Copyright © 2017 Elsevier Inc. All rights reserved.
Observation of Scaling Violations in Scaled Momentum Distributions at HERA
Charged particle production has been measured in deep inelastic scattering
(DIS) events over a large range of and using the ZEUS detector. The
evolution of the scaled momentum, , with in the range 10 to 1280
, has been investigated in the current fragmentation region of the Breit
frame. The results show clear evidence, in a single experiment, for scaling
violations in scaled momenta as a function of .Comment: 21 pages including 4 figures, to be published in Physics Letters B.
Two references adde
D* Production in Deep Inelastic Scattering at HERA
This paper presents measurements of D^{*\pm} production in deep inelastic
scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The
data have been taken with the ZEUS detector at HERA. The decay channel
(+ c.c.) has been used in the study. The
cross section for inclusive D^{*\pm} production with
and is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region
{ GeV and }. Differential cross
sections as functions of p_T(D^{*\pm}), and are
compared with next-to-leading order QCD calculations based on the photon-gluon
fusion production mechanism. After an extrapolation of the cross section to the
full kinematic region in p_T(D^{*\pm}) and (D^{*\pm}), the charm
contribution to the proton structure function is
determined for Bjorken between 2 10 and 5 10.Comment: 17 pages including 4 figure
Surface effects in nucleation and growth of smectic B crystals in thin samples
We present an experimental study of the surface effects (interactions with
the container walls) during the nucleation and growth of smectic B crystals
from the nematic in free growth and directional solidification of a mesogenic
molecule () called CCH4 in thin (of thickness in the 10
m range) samples. We follow the dynamics of the system in real time with a
polarizing microscope. The inner surfaces of the glass-plate samples are coated
with polymeric films, either rubbed polyimid (PI) films or monooriented
poly(tetrafluoroethylene) (PTFE) films deposited by friction at high
temperature. The orientation of the nematic and the smectic B is planar. In
PI-coated samples, the orientation effect of SmB crystals is mediated by the
nematic, whereas, in PTFE-coated samples, it results from a homoepitaxy
phenomenon occurring for two degenerate orientations. A recrystallization
phenomenon partly destroys the initial distribution of crystal orientations. In
directional solidification of polycrystals in PTFE-coated samples, a particular
dynamics of faceted grain boundary grooves is at the origin of a dynamical
mechanism of grain selection. Surface effects also are responsible for the
nucleation of misoriented terraces on facets and the generation of lattice
defects in the solid.Comment: 15 pages, 24 figures, submitted to PR
Nutrient regulation of the islet epigenome controls adaptive insulin secretion
Adaptation of the islet β-cell insulin secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β-cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme Lysine-specific demethylase 1 (Lsd1) in islets. β-cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome
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