The Risk of Posttraumatic Stress Disorder After Trauma Depends on Traumatic Load and the Catechol-O-Methyltransferase Val158Met Polymorphism

The risk for posttraumatic stress disorder (PTSD) depends on the number of traumatic event types experienced in a dose-response relationship, but genetic factors are known to also influence the risk of PTSD. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been found to affect fear extinction and might play a role in the etiology of anxiety disorders.

A delay in consolidation is observed in a heterozygous conditional BMP2 deficient mouse model of distraction osteogenesis

Simultaneous Measurements of Solvent Dynamics and Functional Kinetics in a Light-Activated Enzyme

Solvent fluctuations play a key role in controlling protein motions and biological function. Here, we have studied how individual steps of the reaction catalyzed by the light-activated enzyme protochlorophyllide oxidoreductase (POR) couple with solvent dynamics. To simultaneously monitor the catalytic cycle of the enzyme and the dynamical behavior of the solvent, we designed temperature-dependent UV-visible microspectrophotometry experiments, using flash-cooled nanodroplets of POR to which an exogenous soluble fluorophore was added. The formation and decay of the first two intermediates in the POR-catalyzed reaction were measured, together with the solvent glass transition and the buildup of crystalline ice at cryogenic temperatures. We find that formation of the first intermediate occurs below the glass transition temperature (T(g)), and is not affected by changes in solvent dynamics induced by modifying the glycerol content. In contrast, formation of the second intermediate occurs above T(g) and is influenced by changes in glycerol concentration in a manner remarkably similar to the buildup of crystalline ice. These results suggest that internal, nonslaved protein motions drive the first step of the POR-catalyzed reaction whereas solvent-slaved motions control the second step. We propose that the concept of solvent slaving applies to complex enzymes such as POR.

Structural Basis For The Coupling Between Activation And Inactivation Gating In Potassium Channels

Single-molecule Fluorescence Microscopy Study Of The Ribosome Translation Process

The Role of ILT Mutations in Individual Subunits

Redistribution Of The Human Mu-opioid Receptor (hMor) In HEK 293 Cell Membranes In Response To Agonists

The True Ionic Nature of the Na+/Glucose Cotransporter Leak Current

Specific Interactions of Clausin, a New Lantibiotic, with Lipid Precursors of the Bacterial Cell Wall

We investigated the specificity of interaction of a new type A lantibiotic, clausin, isolated from Bacillus clausii, with lipid intermediates of bacterial envelope biosynthesis pathways. Isothermal calorimetry and steady-state fluorescence anisotropy (with dansylated derivatives) identified peptidoglycan lipids I and II, embedded in dodecylphosphocholine micelles, as potential targets. Complex formation with dissociation constants of approximately 0.3 muM and stoichiometry of approximately 2:1 peptides/lipid intermediate was observed. The interaction is enthalpy-driven. For the first time, to our knowledge, we evidenced the interaction between a lantibiotic and C(55)-PP-GlcNAc, a lipid intermediate in the biosynthesis of other bacterial cell wall polymers, including teichoic acids. The pyrophosphate moiety of these lipid intermediates was crucial for the interaction because a strong binding with undecaprenyl pyrophosphate, accounting for 80% of the free energy of binding, was observed. No binding occurred with the undecaprenyl phosphate derivative. The pentapeptide and the N-acetylated sugar moieties strengthened the interaction, but their contributions were weaker than that of the pyrophosphate group. The lantibiotic decreased the mobility of the pentapeptide. Clausin did not interact with the water-soluble UDP-MurNAc- and pyrophosphoryl-MurNAc-pentapeptides, pointing out the importance of the hydrocarbon chain of the lipid target.

Polarization-Sensitive Two-Photon Microscopy Study of the Organization of Liquid-Crystalline DNA

Highly concentrated DNA solutions exhibit self-ordering properties such as the generation of liquid-crystalline phases. Such organized domains may play an important role in the global chromatin topology but can also be used as a simple model for the study of more complex 3D DNA structures. In this work, using polarized two-photon fluorescence microscopy, we report on the orientation of DNA molecules in liquid-crystalline phases. For this purpose, we analyze the signal emitted by fluorophores that are noncovalently bound to DNA strands. In nonlinear processes, excitation occurs exclusively in the focal volume, which offers advantages such as the reduction of photobleaching of out-of-focus molecules and intrinsic 3D sectioning capability. Propidium iodide and Hoechst, two fluorophores with different DNA binding modes, have been considered. Polarimetric measurements show that the dyes follow the alignment with respect to the DNA strands and allow the determination of the angles between the emission dipoles and the longitudinal axis of the DNA double strand. These results provide a useful starting point toward the application of two-photon polarimetry techniques to determine the local orientation of condensed DNA in physiological conditions.