Analysis of β-globin chromatin micro-environment using a novel 3C variant, 4Cv

Copyright: © 2010 Pink et al.Higher order chromatin folding is critical to a number of developmental processes, including the regulation of gene expression. Recently developed biochemical techniques such as RNA TRAP and chromosome conformation capture (3C) have provided us with the tools to probe chromosomal structures. These techniques have been applied to the β-globin locus, revealing a complex pattern of interactions with regions along the chromosome that the gene resides on. However, biochemical and microscopy data on the nature of β-globin interactions with other chromosomes is contradictory. Therefore we developed a novel 4C variant, Complete-genome 3C by vectorette amplification (4Cv), which allows an unbiased and quantitative method to examine chromosomal structure. We have used 4Cv to study the microenvironment of the β-globin locus in mice and show that a significant proportion of the interactions of β-globin are inter-chromosomal. Furthermore, our data show that in the liver, where the gene is active, β-globin is more likely to interact with other chromosomes, compared to the brain where the gene is silent and is more likely to interact with other regions along the same chromosome. Our data suggest that transcriptional activation of the β-globin locus leads to a change in nuclear position relative to the chromosome territory.Ryan Pink is supported by a grant from Action Medical Research; Daniel Caley is supported by a grant from The Dunhill Medical Trust; David Carter is supported by a grant from the British Society for Haematology

Variable pitch fan system for NASA/Navy research and technology aircraft

Preliminary design of a shaft driven, variable-pitch lift fan and lift-cruise fan was conducted for a V/STOL Research and Technology Aircraft. The lift fan and lift-cruise fan employed a common rotor of 157.5 cm diameter, 1.18 pressure ratio variable-pitch fan designed to operate at a rotor-tip speed of 284 mps. Fan performance maps were prepared and detailed aerodynamic characteristics were established. Cost/weight/risk trade studies were conducted for the blade and fan case. Structural sizing was conducted for major components and weights determined for both the lift and lift-cruise fans

Ethyl and isopropyl 4-ferrocenylbenzoate.

The title compounds, [Fe(C5H5)(C14H13O2)] and [Fe(C5H5)- (C15H15O2)], respectively, contain the ferrocenyl 5(C5H4) and phenylene ±C6H4± rings in a nearly coplanar arrangement, with interplanar angles of 6.88 (12) and 10.5 (2), respectively. Molecules of the ethyl ester form dimers through 5(C5H5)CÐ H O C hydrogen bonds, with graph set R22 (20), and, together with Csp3ÐH (C5H5) interactions, generate a one-dimensional column (irregular ladder). Molecules of the isopropyl ester aggregate through 5(C5H5)CÐH (C6H4) interactions

Differential Effects of Buffer pH On Ca\u3csup\u3e2+\u3c/sup\u3e-Induced ROS Emission with Inhibited Mitochondrial Complexes I and III

Excessive mitochondrial reactive oxygen species (ROS) emission is a critical component in the etiology of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR) injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca2+, a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complexes I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rotenone, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore (mPTP). These results indicate that ROS production by complex I and by complex III is differently affected by buffer pH and Ca2+ loading with mPTP opening. The study suggests that changes in the levels of cytosolic Ca2+ and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III

Heavy and Light Quarks with Lattice Chiral Fermions

The feasibility of using lattice chiral fermions which are free of $O(a)$ errors for both the heavy and light quarks is examined. The fact that the effective quark propagators in these fermions have the same form as that in the continuum with the quark mass being only an additive parameter to a chirally symmetric antihermitian Dirac operator is highlighted. This implies that there is no distinction between the heavy and light quarks and no mass dependent tuning of the action or operators as long as the discretization error $O(m^2 a^2)$ is negligible. Using the overlap fermion, we find that the $O(m^2a^2)$ (and $O(ma^2)$) errors in the dispersion relations of the pseudoscalar and vector mesons and the renormalization of the axial-vector current and scalar density are small. This suggests that the applicable range of $ma$ may be extended to $\sim 0.56$ with only 5% error, which is a factor of $\sim 2.4$ larger than that of the improved Wilson action. We show that the generalized Gell-Mann-Oakes-Renner relation with unequal masses can be utilized to determine the finite $ma$ errors in the renormalization of the matrix elements for the heavy-light decay constants and semileptonic decay constants of the B/D meson.Comment: final version to appear in Int. Jou. Mod. Phys.

Validation of the inverted adsorption structure for free-base tetraphenyl porphyrin on Cu(111)

Utilising normal incidence X-ray standing waves we rigourously scrutinise the “inverted model” as the adsorption structure of free-base tetraphenyl porphyrin on Cu(111). We demonstrate that the iminic N atoms are anchored at near-bridge adsorption sites on the surface displaced laterally by 1.1 ± 0.2 Å in excellent agreement with previously published calculations

Non-Linear Effects in Non-Kerr spacetimes

There is a chance that the spacetime around massive compact objects which are expected to be black holes is not described by the Kerr metric, but by a metric which can be considered as a perturbation of the Kerr metric. These non-Kerr spacetimes are also known as bumpy black hole spacetimes. We expect that, if some kind of a bumpy black hole exists, the spacetime around it should possess some features which will make the divergence from a Kerr spacetime detectable. One of the differences is that these non-Kerr spacetimes do not posses all the symmetries needed to make them integrable. We discuss how we can take advantage of this fact by examining EMRIs into the Manko-Novikov spacetime.Comment: 8 pages, 3 Figures; to appear in the proceedings of the conference "Relativity and Gravitation: 100 Years after Einstein in Prague" (2012

The role of transposable elements in the evolution of aluminium resistance in plants.

Abstract Aluminium (Al) toxicity can severely reduce root growth and consequently affect plant development and yield. A mechanism by which many species resist the toxic effects of Al relies on the efflux of organic anions (OAs) from the root apices via OA transporters. Several of the genes encoding these OA transporters contain transposable elements (TEs) in the coding sequences or in flanking regions. Some of the TE-induced mutations impact Al resistance by modifying the level and/or location of gene expression so that OA efflux from the roots is increased. The importance of genomic modifications for improving the adaptation of plants to acid soils has been raised previously, but the growing number of examples linking TEs with these changes requires highlighting. Here, we review the role of TEs in creating genetic modifications that enhance the adaptation of plants to acid soils by increasing the release of OAs from the root apices. We argue that TEs have been an important source of beneficial mutations that have co-opted OA transporter proteins with other functions to perform this role. These changes have occurred relatively recently in the evolution of many species and likely facilitated their expansion into regions with acidic soils