Role of Histone Tails in Structural Stability of the Nucleosome

Histone tails play an important role in nucleosome structure and dynamics. Here we investigate the effect of truncation of histone tails H3, H4, H2A and H2B on nucleosome structure with 100 ns all-atom molecular dynamics simulations. Tail domains of H3 and H2B show propensity of -helics formation during the intact nucleosome simulation. On truncation of H4 or H2B tails no structural change occurs in histones. However, H3 or H2A tail truncation results in structural alterations in the histone core domain, and in both the cases the structural change occurs in the H2A3 domain. We also find that the contacts between the histone H2A C terminal docking domain and surrounding residues are destabilized upon H3 tail truncation. The relation between the present observations and corresponding experiments is discussed

The Role of Methylation in the Intrinsic Dynamics of B- and Z-DNA

Methylation of cytosine at the 5-carbon position (5mC) is observed in both prokaryotes and eukaryotes. In humans, DNA methylation at CpG sites plays an important role in gene regulation and has been implicated in development, gene silencing, and cancer. In addition, the CpG dinucleotide is a known hot spot for pathologic mutations genome-wide. CpG tracts may adopt left-handed Z-DNA conformations, which have also been implicated in gene regulation and genomic instability. Methylation facilitates this B-Z transition but the underlying mechanism remains unclear. Herein, four structural models of the dinucleotide d(GC)5 repeat sequence in B-, methylated B-, Z-, and methylated Z-DNA forms were constructed and an aggregate 100 nanoseconds of molecular dynamics simulations in explicit solvent under physiological conditions was performed for each model. Both unmethylated and methylated B-DNA were found to be more flexible than Z-DNA. However, methylation significantly destabilized the BII, relative to the BI, state through the Gp5mC steps. In addition, methylation decreased the free energy difference between B- and Z-DNA. Comparisons of α/γ backbone torsional angles showed that torsional states changed marginally upon methylation for B-DNA, and Z-DNA. Methylation-induced conformational changes and lower energy differences may contribute to the transition to Z-DNA by methylated, over unmethylated, B-DNA and may be a contributing factor to biological function

MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury

Spinal cord injury (SCI) triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of microRNAs, short non-coding RNA molecules that repress the translation of target mRNA. To understand the mechanisms underlying gene alterations following SCI, we analyzed the microRNA expression patterns at different time points following rat spinal cord injury

TRANSITION CHARGE-DENSITIES OF LOW-LYING COLLECTIVE STATES IN PT 196 FROM INELASTIC ELECTRON-SCATTERING

Differential cross sections for levels in the excitation-energy range from 0 to 3.0 MeV in Pt-196 have been measured by inelastic electron scattering in a momentum-transfer range up to 2.5 fm-1. The ground-state charge density and the transition charge densities of nine low-lying collective levels have been extracted in a Fourier-Bessel analysis of these data. The densities are compared with those obtained from microscopic calculations within the quasiparticle phonon model, using the single-particle basis obtained from a density functional approach. Satisfactory agreement has been obtained, in spite of the complicated structure of Pt-196

STRENGTH DISTRIBUTIONS IN NEODYMIUM ISOTOPES - A TEST OF COLLECTIVE NUCLEAR-MODELS

Excite states n even N isotopes, up to excitation energies of 3-4 MeV, were investigate in proton- and deuteron-scattering experiments performed with high-energy resolution. More than 300 transitions were studied. For several new excited states spin and parity assignments have been suggested. Reduced transition probabilities were extracted for natural-parity states from 0+ up to 6+. The experimental strength distributions have been compared with the predictions of the interacting boson model (IBM) and of the quasi-particle-phonon model (QPM). The octupole transition probabilities are well described in both models as produced by the fragmentation of the f-boson or of E3 phonons. IBM-sdf calculations seem to account also for the transitions to the low-lying 1- states. Quadrupole and hexadecapole distributions are well described in the QPM. The leading configurations are due to 6-8 low-lying one-phonon states. The two- and three-phonon states play an important role especially in Nd-146. The failure of IBM quadrupole and hexadecapole calculations clearly points out the need of introducing additional bosons lying at high excitation energies. QPM evaluations account also for other features of the experimental data, as the E5 and E6 strength distributions and the isovector components. The limits of the two models are discussed

Particle-hole and particle-particle correlations in neodymium isotopes

Excited states in Nd-140,Nd-142,Nd-144,Nd-146 nuclei, up to an excitation energy of about 5 MeV, were investigated by (p,t) experiments performed with a good energy resolution. These data, together with proton and deuteron scattering data from a previous experiment, are compared with Quasi-Particle Phonon Model evaluations, in which the competition between particle-hole and particle-particle residual interactions is considered. The B(E lambda) distributions are satisfactorily reproduced. The Nd-146,Nd-148(p,t) reaction data are well accounted for, while difficulties are found in reproducing those for Nd-142,Nd-144(p,t). Limitations and improvements of the model are discussed.</p