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The spliceosome is a dynamic ribonucleoprotein (RNP) machine that catalyzes the removal of introns during the two transesterification steps of eukaryotic pre-mRNA splicing. Here we used single-molecule fluorescence resonance energy transfer to monitor the distance of the 5' splice site (5' SS) and branch point (BP) of pre-mRNA in affinity-purified(More)
Large earthquakes produce crustal deformation that can be quantified by geodetic measurements, allowing for the determination of the slip distribution on the fault. We used data from Global Positioning System (GPS) networks in Central Chile to infer the static deformation and the kinematics of the 2010 moment magnitude (M(w)) 8.8 Maule megathrust(More)
Many long non-coding RNAs (lncRNAs) affect gene expression, but the mechanisms by which they act are still largely unknown. One of the best-studied lncRNAs is Xist, which is required for transcriptional silencing of one X chromosome during development in female mammals. Despite extensive efforts to define the mechanism of Xist-mediated transcriptional(More)
AIMS With an estimated 12 million consumers in Europe, cocaine (COC) is the illicit drug leading to the most emergency department visits. The aim of this study was to examine a consecutive series of sudden deaths (SDs) to focus on the prevalence, the toxicological characteristics, and the causes of death in COC-related fatalities. METHODS AND RESULTS(More)
We propose a general approach for determining the entropy and free energy of complex systems as a function of temperature and pressure. In this method the Fourier transform of the velocity autocorrelation function, obtained from a short ͑20 ps͒ molecular dynamics trajectory is used to obtain the vibrational density of states ͑DoS͒ which is then used to(More)
The spliceosome is a complex small nuclear RNA (snRNA)-protein machine that removes introns from pre-mRNAs via two successive phosphoryl transfer reactions. The chemical steps are isoenergetic, yet splicing requires at least eight RNA-dependent ATPases responsible for substantial conformational rearrangements. To comprehensively monitor pre-mRNA(More)
Single-molecule methods have given researchers the ability to investigate the structural dynamics of biomolecules at unprecedented resolution and sensitivity. One of the preferred methods of studying single biomolecules is single-molecule fluorescence resonance energy transfer (smFRET). The popularity of smFRET stems from its ability to report on dynamic,(More)
During pre-mRNA splicing, a central step in the expression and regulation of eukaryotic genes, the spliceosome selects splice sites for intron excision and exon ligation. In doing so, the spliceosome must distinguish optimal from suboptimal splice sites. At the catalytic stage of splicing, suboptimal splice sites are repressed by the DEAH-box ATPases Prp16(More)
The Xist long noncoding RNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly(More)
The effect of molecular architecture of a surfactant, particularly the attachment position of benzene sulfonate on the hexadecane backbone, at the decane-water interface was investigated using atomistic MD simulations. We consider a series of surfactant isomers in the family of alkyl benzene sulfonates, denoted by m-C16, indicating a benzene sulfonate group(More)