The k-junction motif in RNA structure

The k-junction is a structural motif in RNA comprising a three-way helical junction based upon kink turn (k-turn) architecture. A computer program written to examine relative helical orientation identified the three-way junction of the Arabidopsis TPP riboswitch as an elaborated k-turn. The Escherichia coli TPP riboswitch contains a related k-junction, and analysis of >11 000 sequences shows that the structure is common to these riboswitches. The k-junction exhibits all the key features of an N1-class k-turn, including the standard cross-strand hydrogen bonds. The third helix of the junction is coaxially aligned with the C (canonical) helix, while the k-turn loop forms the turn into the NC (non-canonical) helix. Analysis of ligand binding by ITC and global folding by gel electrophoresis demonstrates the importance of the k-turn nucleotides. Clearly the basic elements of k-turn structure are structurally well suited to generate a three-way helical junction, retaining all the key features and interactions of the k-turn

Intrinsic noise in systems with switching environments

We study individual-based dynamics in finite populations, subject to randomly switching environmental conditions. These are inspired by models in which genes transition between on and off states, regulating underlying protein dynamics. Similarly switches between environmental states are relevant in bacterial populations and in models of epidemic spread. Existing piecewise-deterministic Markov process (PDMP) approaches focus on the deterministic limit of the population dynamics while retaining the randomness of the switching. Here we go beyond this approximation and explicitly include effects of intrinsic stochasticity at the level of the linear-noise approximation. Specifically we derive the stationary distributions of a number of model systems, in good agreement with simulations. This improves existing approaches which are limited to the regimes of fast and slow switching.Comment: 15 pages, 11 figure

A stochastic and dynamical view of pluripotency in mouse embryonic stem cells

Pluripotent embryonic stem cells are of paramount importance for biomedical research thanks to their innate ability for self-renewal and differentiation into all major cell lines. The fateful decision to exit or remain in the pluripotent state is regulated by complex genetic regulatory network. Latest advances in transcriptomics have made it possible to infer basic topologies of pluripotency governing networks. The inferred network topologies, however, only encode boolean information while remaining silent about the roles of dynamics and molecular noise in gene expression. These features are widely considered essential for functional decision making. Herein we developed a framework for extending the boolean level networks into models accounting for individual genetic switches and promoter architecture which allows mechanistic interrogation of the roles of molecular noise, external signaling, and network topology. We demonstrate the pluripotent state of the network to be a broad attractor which is robust to variations of gene expression. Dynamics of exiting the pluripotent state, on the other hand, is significantly influenced by the molecular noise originating from genetic switching events which makes cells more responsive to extracellular signals. Lastly we show that steady state probability landscape can be significantly remodeled by global gene switching rates alone which can be taken as a proxy for how global epigenetic modifications exert control over stability of pluripotent states.Comment: 11 pages, 7 figure

The first measurement of BB meson semi-leptonic decay contribution to non-photonic electrons at RHIC

We present the first measurement for the $B$ meson semi-leptonic decay contribution to non-photonic electrons at RHIC using non-photonic electron azimuthal correlations with charged hadrons in p+p collisions at $\sqrt{s_{NN}} = 200$ GeV from STAR.Comment: 4 pages, 3 figures, Quark Matter 2006 Proceedings, to appear in J. Phys.

Sleep Endoscopy in the Evaluation of Pediatric Obstructive Sleep Apnea

Pediatric obstructive sleep apnea (OSA) is not always resolved or improved with adenotonsillectomy. Persistent or complex cases of pediatric OSA may be due to sites of obstruction in the airway other than the tonsils and adenoids. Identifying these areas in the past has been problematic, and therefore, therapy for OSA in children who have failed adenotonsillectomy has often been unsatisfactory. Sleep endoscopy is a technique that can enable the surgeon to determine the level of obstruction in a sleeping child with OSA. With this knowledge, site-specific surgical therapy for persistent and complex pediatric OSA may be possible

Modeling the Effects of Drug Binding on the Dynamic Instability of Microtubules

We propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady state microtubules assembled from MAP-free tubulin. Both experimentally and theoretically we study the perturbation of microtubule dynamic instability by S-methyl-D-DM1, a synthetic derivative of the microtubule-targeted agent maytansine and a potential anticancer agent. We find that to be an effective suppressor of microtubule dynamics a drug must primarily suppress the loss of GDP tubulin from the microtubule tip.Comment: 17 pages, 11 figures, to appear in Phys. Bio

Salicylaldehyde hydrazones: buttressing of outer sphere hydrogen-bonding and copper-extraction properties

Salicylaldehyde hydrazones are weaker copper extractants than their oxime derivatives, which are used in hydrometallurgical processes to recover ~20 % of the world’s copper. Their strength, based on the extraction equilibrium constant Ke, can be increased by nearly three orders of magnitude by incorporating electron-withdrawing or hydrogen-bond acceptor groups (X) ortho to the phenolic OH group of the salicylaldehyde unit. Density functional theory calculations suggest that the effects of the 3-X substituents arise from a combination of their influence on the acidity of the phenol in the pH-dependent equilibrium, Cu2+ + 2Lorg ⇌ [Cu(L–H)2]org + 2H+, and on their ability to ‘buttress’ interligand hydrogen bonding by interacting with the hydrazone N–H donor group. X-ray crystal structure determination and computed structures indicate that in both the solid state and the gas phase, coordinated hydrazone groups are less planar than coordinated oximes and this has an adverse effect on intramolecular hydrogen-bond formation to the neighbouring phenolate oxygen atoms

Magnetic field diagnostics and spatio-temporal variability of the solar transition region

Magnetic field diagnostics of the transition region from the chromosphere to the corona faces us with the problem that one has to apply extreme UV spectro-polarimetry. While for coronal diagnostic techniques already exist through infrared coronagraphy above the limb and radio observations on the disk, for the transition region one has to investigate extreme UV observations. However, so far the success of such observations has been limited, but there are various projects to get spectro-polarimetric data in the extreme UV in the near future. Therefore it is timely to study the polarimetric signals we can expect for such observations through realistic forward modeling. We employ a 3D MHD forward model of the solar corona and synthesize the Stokes I and Stokes V profiles of C IV 1548 A. A signal well above 0.001 in Stokes V can be expected, even when integrating for several minutes in order to reach the required signal-to-noise ratio, despite the fact that the intensity in the model is rapidly changing (just as in observations). Often this variability of the intensity is used as an argument against transition region magnetic diagnostics which requires exposure times of minutes. However, the magnetic field is evolving much slower than the intensity, and thus when integrating in time the degree of (circular) polarization remains rather constant. Our study shows the feasibility to measure the transition region magnetic field, if a polarimetric accuracy on the order of 0.001 can be reached, which we can expect from planned instrumentation.Comment: Accepted for publication in Solar Physics (4.Mar.2013), 19 pages, 9 figure