Novel complex MAD phasing and RNase H structural insights using selenium oligonucleotides

The crystal structures of protein–nucleic acid complexes are commonly determined using selenium-derivatized proteins via MAD or SAD phasing. Here, the first protein–nucleic acid complex structure determined using selenium-derivatized nucleic acids is reported. The RNase H–RNA/DNA complex is used as an example to demonstrate the proof of principle. The high-resolution crystal structure indicates that this selenium replacement results in a local subtle unwinding of the RNA/DNA substrate duplex, thereby shifting the RNA scissile phosphate closer to the transition state of the enzyme-catalyzed reaction. It was also observed that the scissile phosphate forms a hydrogen bond to the water nucleophile and helps to position the water molecule in the structure. Consistently, it was discovered that the substitution of a single O atom by a Se atom in a guide DNA sequence can largely accelerate RNase H catalysis. These structural and catalytic studies shed new light on the guide-dependent RNA cleavage

Opacity in compact extragalactic radio sources and its effect on astrophysical and astrometric studies

The apparent position of the "core" in a parsec-scale radio jet (a compact, bright emitting region at the narrow end of the jet) depends on the observing frequency, owing to synchrotron self-absorption and external absorption. While providing a tool probing physical conditions in the vicinity of the core, this dependency poses problems for astrometric studies using compact radio sources. We investigated the frequency-dependent shift in the positions of the cores (core shift) observed with very long baseline interferometry (VLBI) in parsec-scale jets. We discuss related physics, as well as its effect on radio astrometry and the connection between radio and optical positions of astrometric reference objects. We searched for the core shift in a sample of 277 radio sources imaged at 2.3 GHz (13 cm) and 8.6 GHz (4 cm) frequency bands using VLBI observations made in 2002 and 2003. The core shift was measured by referencing the core position to optically thin jet features whose positions are not expected to change with frequency. We present here results for 29 selected active galactic nuclei (AGN) with bright distinct VLBI jet features that can be used in differential measurements and that allow robust measurements of the shift to be made. In these AGN, the magnitude of the measured core shift between 2.3 and 8.6 GHz reaches 1.4 mas, with a median value for the sample of 0.44 mas. Nuclear flares result in temporal variability of the shift. An average shift between the radio (4 cm) and optical (6000 Angstrom) bands is estimated to be approximately 0.1 mas, and it should be taken into account in order to provide the required accuracy of the radio-optical reference frame connection. This can be accomplished with multi-frequency VLBI measurements... (abridged)Comment: 11 pages, 8 figures, 2 tables, accepted for publication in the Astronomy and Astrophysics; minor corrections to the manuscript are mad

Towards digital cohomology

We propose a method for computing the Z 2–cohomology ring of a simplicial complex uniquely associated with a three–dimensional digital binary–valued picture I. Binary digital pictures are represented on the standard grid Z 3, in which all grid points have integer coordinates. Considering a particular 14–neighbourhood system on this grid, we construct a unique simplicial complex K(I) topologically representing (up to isomorphisms of pictures) the picture I. We then compute the cohomology ring on I via the simplicial complex K(I). The usefulness of a simplicial description of the digital Z 2–cohomology ring of binary digital pictures is tested by means of a small program visualizing the different steps of our method. Some examples concerning topological thinning, the visualization of representative generators of cohomology classes and the computation of the cup product on the cohomology of simple 3D digital pictures are showed

Sufficient conditions for topological invariance of 2D images under rigid transformations

International audienceIn ℝ^2, rigid transformations are topology-preserving operations. However, this property is generally no longer true when considering digital images instead of continuous ones, due to digitization effects. In this article, we investigate this issue by studying discrete rigid transformations (DRTs) on ℤ^2. More precisely, we define conditions under which digital images preserve their topological properties under any arbitrary DRTs. Based on the recently introduced notion of DRT graph and the classical notion of simple point, we first identify a family of local patterns that authorize topological invariance under DRTs. These patterns are then involved in a local analysis process that guarantees topological invariance of whole digital images in linear time

Kinematics of the outer pseudorings and the spiral structure of the Galaxy

The kinematics of the outer rings and pseudorings is determined by two processes: the resonance tuning and the gas outflow. The resonance kinematics is clearly observed in the pure rings, while the kinematics of the gas outflow is manifested itself in the pseudorings. The direction of systematical motions in the pure rings depends on the position angle of a point with respect to the bar major axis and on the class of the outer ring. The direction of the radial and azimuthal components of the residual velocities of young stars in the Perseus, Carina, and Sagittarius regions can be explained by the presence of the outer pseudoring of class R1R2' in the Galaxy. We present models, which reproduce the directions and values of the residual velocities of OB-associations in the Perseus and Sagittarius regions, and also model reproducing the directions of the residual velocities in the Perseus, Sagittarius, and Carina regions. The kinematics of the Sagittarius region accurately defines the solar position angle with respect to the bar elongation, theta_b=45 (+/-5) deg.Comment: 16 pages, 10 figures, accepted for publication in Astronomy Letter

Characterizing early drug resistance-related events using geometric ensembles from HIV protease dynamics:

The use of antiretrovirals (ARVs) has drastically improved the life quality and expectancy of HIV patients since their introduction in health care. Several millions are still afflicted worldwide by HIV and ARV resistance is a constant concern for both healthcare practitioners and patients, as while treatment options are finite, the virus constantly adapts via complex mutation patterns to select for resistant strains under the pressure of drug treatment. The HIV protease is a crucial enzyme for viral maturation and has been a game changing drug target since the first application. Due to similarities in protease inhibitor designs, drug cross-resistance is not uncommon across ARVs of the same class