Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line

Butyrate, a known histone deacetylase inhibitor (HDACi) and product of fibre fermentation, is postulated to mediate the protective effect of dietary fibre against colon cancer. The transcription factor Sp1 is a target of acetylation and is known to be associated with class I HDACs, including HDAC1. Sp1 is a ubiquitous transcription factor and Sp1-regulated genes include those involved in cell cycle regulation, apoptosis and lipogenesis: all major pathways in cancer development. The only known acetylated residue of Sp1 is lysine703 which resides in the DNA binding domain. Here we show that acetylated Sp1 loses p21- and bak-promoter -binding function in vitro. Furthermore treatment with a panel of HDAC inhibitors showed clustering of activities for a subset of inhibitors, causing G2 cell cycle arrest, Sp1 acetylation, p21 and Bak over-expression, all with very similar EC50 concentrations. These HDACi activities were not distributed according to the molecular class of compound. In order to mimic loss of binding, an siRNA strategy was used to reduce Sp1 expression. This resulted in altered expression of multiple elements of the p53/p21 pathway. Taken together our data suggest a mechanistic model for the chemopreventive actions of butyrate in colon epithelial cells, and provide new insight into the differential activities some classes of HDAC inhibitors

The effect of rare regions on a disordered itinerant quantum antiferromagnet with cubic anisotropy

We study the quantum phase transition of an itinerant antiferromagnet with cubic anisotropy in the presence of quenched disorder, paying particular attention to the locally ordered spatial regions that form in the Griffiths region. We derive an effective action where these rare regions are described in terms of static annealed disorder. A one loop renormalization group analysis of the effective action shows that for order parameter dimensions $p<4$ the rare regions destroy the conventional critical behavior. For order parameter dimensions $p>4$ the critical behavior is not influenced by the rare regions, it is described by the conventional dirty cubic fixed point. We also discuss the influence of the rare regions on the fluctuation-driven first-order transition in this system.Comment: 6 pages RevTe

Dynamic Scaling in Diluted Systems Phase Transitions: Deactivation trough Thermal Dilution

Activated scaling is confirmed to hold in transverse field induced phase transitions of randomly diluted Ising systems. Quantum Monte Carlo calculations have been made not just at the percolation threshold but well bellow and above it including the Griffiths-McCoy phase. A novel deactivation phenomena in the Griffiths-McCoy phase is observed using a thermal (in contrast to random) dilution of the system.Comment: 4 pages, 4 figures, RevTe

Griffiths-McCoy Singularities in the Random Transverse-Field Ising Spin Chain

We consider the paramagnetic phase of the random transverse-field Ising spin chain and study the dynamical properties by numerical methods and scaling considerations. We extend our previous work [Phys. Rev. B 57, 11404 (1998)] to new quantities, such as the non-linear susceptibility, higher excitations and the energy-density autocorrelation function. We show that in the Griffiths phase all the above quantities exhibit power-law singularities and the corresponding critical exponents, which vary with the distance from the critical point, can be related to the dynamical exponent z, the latter being the positive root of [(J/h)^{1/z}]_av=1. Particularly, whereas the average spin autocorrelation function in imaginary time decays as [G]_av(t)~t^{-1/z}, the average energy-density autocorrelations decay with another exponent as [G^e]_av(t)~t^{-2-1/z}.Comment: 8 pages RevTeX, 8 eps-figures include

Correlated disordered interactions on Potts models

Using a weak-disorder scheme and real-space renormalization-group techniques, we obtain analytical results for the critical behavior of various q-state Potts models with correlated disordered exchange interactions along d1 of d spatial dimensions on hierarchical (Migdal-Kadanoff) lattices. Our results indicate qualitative differences between the cases d-d1=1 (for which we find nonphysical random fixed points, suggesting the existence of nonperturbative fixed distributions) and d-d1>1 (for which we do find acceptable perturbartive random fixed points), in agreement with previous numerical calculations by Andelman and Aharony. We also rederive a criterion for relevance of correlated disorder, which generalizes the usual Harris criterion.Comment: 8 pages, 4 figures, to be published in Physical Review

The signed loop approach to the Ising model: foundations and critical point

The signed loop method is a beautiful way to rigorously study the two-dimensional Ising model with no external field. In this paper, we explore the foundations of the method, including details that have so far been neglected or overlooked in the literature. We demonstrate how the method can be applied to the Ising model on the square lattice to derive explicit formal expressions for the free energy density and two-point functions in terms of sums over loops, valid all the way up to the self-dual point. As a corollary, it follows that the self-dual point is critical both for the behaviour of the free energy density, and for the decay of the two-point functions.Comment: 38 pages, 7 figures, with an improved Introduction. The final publication is available at link.springer.co

On the critical behavior of disordered quantum magnets: The relevance of rare regions

The effects of quenched disorder on the critical properties of itinerant quantum antiferromagnets and ferromagnets are considered. Particular attention is paid to locally ordered spatial regions that are formed in the presence of quenched disorder even when the bulk system is still in the paramagnetic phase. These rare regions or local moments are reflected in the existence of spatially inhomogeneous saddle points of the Landau-Ginzburg-Wilson functional. We derive an effective theory that takes into account small fluctuations around all of these saddle points. The resulting free energy functional contains a new term in addition to those obtained within the conventional perturbative approach, and it comprises what would be considered non-perturbative effects within the latter. A renormalization group analysis shows that in the case of antiferromagnets, the previously found critical fixed point is unstable with respect to this new term, and that no stable critical fixed point exists at one-loop order. This is contrasted with the case of itinerant ferromagnets, where we find that the previously found critical behavior is unaffected by the rare regions due to an effective long-ranged interaction between the order parameter fluctuations.Comment: 16 pp., REVTeX, epsf, 2 figs, final version as publishe

Smeared phase transition in a three-dimensional Ising model with planar defects: Monte-Carlo simulations

We present results of large-scale Monte Carlo simulations for a three-dimensional Ising model with short range interactions and planar defects, i.e., disorder perfectly correlated in two dimensions. We show that the phase transition in this system is smeared, i.e., there is no single critical temperature, but different parts of the system order at different temperatures. This is caused by effects similar to but stronger than Griffiths phenomena. In an infinite-size sample there is an exponentially small but finite probability to find an arbitrary large region devoid of impurities. Such a rare region can develop true long-range order while the bulk system is still in the disordered phase. We compute the thermodynamic magnetization and its finite-size effects, the local magnetization, and the probability distribution of the ordering temperatures for different samples. Our Monte-Carlo results are in good agreement with a recent theory based on extremal statistics.Comment: 9 pages, 6 eps figures, final version as publishe

Manipulating mitochondrial dynamics in the NTS prevents diet-induced deficits in brown fat morphology and glucose uptake

Aims Brown adipose tissue (BAT) can produce heat by metabolizing glucose and fatty acids. Activation of BAT is controlled by the central nervous system (CNS) through sympathetic innervation. Dysregulation of signalling molecules in selective CNS areas such as the nucleus of tractus solitarius (NTS) are linked with altered BAT activity, obesity and diabetes. High-fat diet (HFD)-feeding increases mitochondrial fragmentation in the NTS, triggering insulin resistance, hyperphagia and weight gain. Here we sought to determine whether changes in mitochondrial dynamics in the NTS can affect BAT glucose uptake. Main methods Rats received DVC stereotactic surgery for local brain administration of viruses that express mutated Drp1 genes. BAT glucose uptake was measured with PET/CT scans. Biochemical assays and immunohistochemistry determined altered levels of key signalling molecules and neural innervation of BAT. Key findings We show that short-term HFD-feeding decreases BAT glucose uptake. However, inhibiting mitochondrial fragmentation in NTS-astrocytes of HFD-fed rats partially restores BAT glucose uptake accompanied by lower blood glucose and insulin levels. Tyrosine Hydroxylase (TH) revealed that rats with inhibited mitochondrial fragmentation in NTS astrocytes had higher levels of catecholaminergic innervation in BAT compared to HFD-fed rats, and did not exhibit HFD-dependent infiltration of enlarged white fat droplets in the BAT. In regular chow-fed rats, increasing mitochondrial fragmentation in the NTS-astrocytes reduced BAT glucose uptake, TH immune-positive boutons and β3-adrenergic receptor levels. Significance Our data suggest that targeting mitochondrial dynamics in the NTS-astrocytes could be a beneficial strategy to increase glucose utilization and protect from developing obesity and diabetes

Ab initio calculations for bromine adlayers on the Ag(100) and Au(100) surfaces: the c(2x2) structure

Ab initio total-energy density-functional methods with supercell models have been employed to calculate the c(2x2) structure of the Br-adsorbed Ag(100) and Au(100) surfaces. The atomic geometries of the surfaces and the preferred bonding sites of the bromine have been determined. The bonding character of bromine with the substrates has also been studied by analyzing the electronic density of states and the charge transfer. The calculations show that while the four-fold hollow-site configuration is more stable than the two-fold bridge-site topology on the Ag(100) surface, bromine prefers the bridge site on the Au(100) surface. The one-fold on-top configuration is the least stable configuration on both surfaces. It is also observed that the second layer of the Ag substrate undergoes a small buckling as a consequence of the adsorption of Br. Our results provide a theoretical explanation for the experimental observations that the adsorption of bromine on the Ag(100) and Au(100) surfaces results in different bonding configurations.Comment: 10 pages, 4 figure, 5 tables, Phys. Rev. B, in pres