Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation

Background: Neuropilin is a transmembrane receptor for vascular endothelial growth factor (VEGF) and is expressed in normal endothelial cells and upregulated in cancer cells. Neuropilin-1 (NRP-1) has been shown to promote tumour cell migration and survival in colon cancer in response to VEGF binding. The expression profiles of neuropilins, associated co-receptors and known ligands have been mapped in three colorectal cell lines: Caco-2, HCT116 & HT29. We have previously shown that butyrate, a naturally occurring histone deacetylase inhibitor (HDACi) produced by fermentation of fibre in the colon, causes apoptosis of colon cancer cell lines. Results: Here we demonstrate that butyrate down-regulates NRP-1 and VEGF at the mRNA and protein level in colorectal cancer cell lines. NRP-1 is a known transcriptional target of Sp1, whose activity is regulated by acetylation. NRP-1 down-regulation by butyrate was associated with decreased binding affinity of Sp1 for canonical Sp-binding sites in the NRP-1 promoter. siRNA-mediated knock-down of Sp1 implied that Sp1 may have strong DNA binding activity but weak transactivation potential. Conclusion: The downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre

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

Class-based Storage With a Finite Number of Items

ABC class-based storage is widely studied in literature and applied practice. It divides all stored items into a limited number of classes according to their demand rates (turnover per unit time). Classes of items with higher turnovers are stored in a region closer to the warehouse depot. In literature, it is commonly shown that the use of more storage classes leads to shorter travel time for storing and retrieving items. A basic assumption in this literature commonly is that the required storage space of items equals their average inventory levels, which is right if an infinite number of items are stored in each storage region. However, if a finite number of items are stored in the warehouse, more storage classes need more space to store the items: more classes lead to fewer items stored per class, which have less opportunity to share space with other items. This paper revisits ABC class-based storage by relaxing the common assumption that the total required storage space of all items is independent of the number of classes. We develop a travel time model and use it for optimizing the number and the boundaries of classes. Our numerical results illustrate that a small number of classes is optimal

Quaternized and Unmodified Chitosans: Hydrodynamic Properties

Molecular properties of N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan (modified chitosan) series with the averaged quaternization degree 90% have been studied in comparison with the unmodified chitosan series by the method of translation isothermal diffusion, viscometry and static light scattering in dilute solutions in 0.33M CH3COOH+0.2M.CH3COONa at pH 3.54. Molecular mass, translation diffusion coefficient, and hydrodynamic size of the homologues samples in the modified/unnmodified series have been determined as well as their chain rigidity and Mark-Kuhn-Houwink equations at acidic pH. It was established that the size of modified chitosan molecules might be smaller than the initial polysaccharide of an equal polymerization degree in the same solvent, which was explained by the change of thermodynamic conditions and the change of the ratio of thermodynamic/electrostatic contributions to the total chain rigidity. Quaternized chitosan molecules displayed the different hydrodynamic behavior in 0.33M CH3COOH+0.2M.CH3COONa and in 0.2M NaCl (neutral pH). Solution properties of quaternized chitosan at neutral pH had been identified as the concentration dependent. The threshold influence of the secondary amino group protonation on the hydrodynamic properties of modified chitosan molecules was detected in 0.2M NaCl at the solute concentration range 0.001-0.004 g/cm3

Forbidden Landscape from Holography

We present a class of field configurations that are forbidden in the quantum gravity because of inconsistency in the dual field theory from holography. Scale invariant but non-conformal field theories are impossible in (1+1) dimension, and so should be the corresponding gravity dual. In particular, the "spontaneous Lorentz symmetry breaking" models and the "ghost condensation" models, which are well-studied in phenomenology literatures, are forbidden in any consistent quantum theories of gravity in (1+2) dimension since they predict such inconsistent field configurations.Comment: 4pages, v2: some improvements, reference adde

Entanglement Sudden Death in Band Gaps

Using the pseudomode method, we evaluate exactly time-dependent entanglement for two independent qubits, each coupled to a non-Markovian structured environment. Our results suggest a possible way to control entanglement sudden death by modifying the qubit-pseudomode detuning and the spectrum of the reservoirs. Particularly, in environments structured by a model of a density-of-states gap which has two poles, entanglement trapping and prevention of entanglement sudden death occur in the weak-coupling regime

Symmetry Theory of the Flexomagnetoelectric Interaction in the Magnetic Vortices and Skyrmions

Symmetry classification of the magnetic vortices and skyrmions has been suggested. Relation between symmetry based predictions and direct calculation has been shown. It was shown, that electric dipole moment of the vortex is located inside the small vortex core. The antivortices and antiskyrmions do not carry the total core electric dipole induced by the flexomagnetoelectric interaction in the hexoctahedral cubic crystal. The volumetric bound electric charge is distributed around the core. Switching of the core electric dipole direction produces the switching of the core magnetization or vortex chirality and vice versa. The vortices and skyrmions with time-invariant enantiomorphism have two degenerative states: clockwise and counterclockwise state.Comment: Submitted revised version to the Physica B: Condenced Matte

Vortex structure in exponentially shaped Josephson junctions

We report the numerical calculations of the static vortex structure and critical curves in exponentially shaped long Josephson junctions for in-line and overlap geometries. Each solution of the corresponding boundary value problem is associated with the Sturm-Liouville problem whose minimal eigenvalue allows to make a conclusion about the stability of the vortex. The change in width of the junction leads to the renormalization of the magnetic flux in comparison to the case of a linear one-dimensional model. We study the influence of the model's parameters and, particularly, the shape parameter on the stability of the states of the magnetic flux. We compare the vortex structure and critical curves for the in-line and overlap geometries. Our numerically constructed critical curve of the Josephson junction matches well with the experimental one.Comment: 8 pages, 10 figures, NATO Advanced Research Workshop on "Vortex dynamics in superconductors and other complex systems" Yalta, Crimea, Ukraine, 13-17 September 200

Cluster of Dipolar Coupled Spins as a Quantum Memory Storage

Spin dynamics of a cluster of coupled spins 1/2 can be manipulated to store and process a large amount of information. A new type of dynamic response makes it possible to excite coherent long-living signals, which can be used for exchanging information with a mesoscopic quantum system. An experimental demonstration is given for a system of 19 proton spins of a liquid crystal molecule.Comment: 5 pages, 1 figur

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