The actin-based molecular motor myosin VI functions in the endocytic uptake pathway, both during the early stages of clathrin-mediated uptake and in later transport to/from early endosomes. This study uses fluorescence recovery after photobleaching (FRAP) to examine the turnover rate of myosin VI during endocytosis. The results demonstrate that myosin VI turns over dynamically on endocytic structures with a characteristic half-life common to both the large insert isoform of myosin VI on clathrin-coated structures and the no-insert isoform on early endosomes. This half-life is shared by the myosin VI-binding partner Dab2 and is identical for full-length myosin VI and the cargo-binding tail region. The 4-fold slower half-life of an artificially dimerized construct of myosin VI on clathrin-coated structures suggests that wild type myosin VI does not function as a stable dimer, but either as a monomer or in a monomer/dimer equilibrium. Taken together, these FRAP results offer insight into both the basic turnover dynamics and the monomer/dimer nature of myosin VI.
Evolutionary constraints which limit the forces produced during bell contractions of medusae affect the overall medusan morphospace such that jet propulsion is limited to only small medusae. Cubomedusae, which often possess large prolate bells and are thought to swim via jet propulsion, appear to violate the theoretical constraints which determine the medusan morphospace. To examine propulsion by cubomedusae, we quantified size related changes in wake dynamics, bell shape, swimming and turning kinematics of two species of cubomedusae, Chironex fleckeri and Chiropsella bronzie. During growth, these cubomedusae transitioned from using jet propulsion at smaller sizes to a rowing-jetting hybrid mode of propulsion at larger sizes. Simple modifications in the flexibility and kinematics of their velarium appeared to be sufficient to alter their propulsive mode. Turning occurs during both bell contraction and expansion and is achieved by generating asymmetric vortex structures during both stages of the swimming cycle. Swimming characteristics were considered in conjunction with the unique foraging strategy used by cubomedusae.
In this work we study the dynamical features of editorial wars in Wikipedia (WP). Based on our previously established algorithm, we build up samples of controversial and peaceful articles and analyze the temporal characteristics of the activity in these samples. On short time scales, we show that there is a clear correspondence between conflict and burstiness of activity patterns, and that memory effects play an important role in controversies. On long time scales, we identify three distinct developmental patterns for the overall behavior of the articles. We are able to distinguish cases eventually leading to consensus from those cases where a compromise is far from achievable. Finally, we analyze discussion networks and conclude that edit wars are mainly fought by few editors only.
Vault particles possess many attributes that can be exploited in nanobiotechnology, particularly in the creation of drug delivery nanodevices. These include self-assembly, 100nm size range, a dynamic structure that may be controlled for manipulation of drug release kinetics and natural presence in humans ensuring biocompatibility. The flexibility and the adaptability of this system have been greatly enhanced by the emerging atomic-level information and improved comprehension of vault structure and dynamics. It seems likely that this information will allow their specific tailoring to the individual requirements of each drug and target tissue. These properties provide vaults with an enormous potential as a versatile delivery platform.
Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. Here we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~ 6-14 nm resolution. The statistical analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.
Maturation of HIV-1 particles encompasses a complex morphological transformation of Gag via an orchestrated series of proteolytic cleavage events. A longstanding question concerns the structure of the C-terminal region of CA and the peptide SP1 (CA-SP1), which represents an intermediate during maturation of the HIV-1 virus. By integrating NMR, cryo-EM, and molecular dynamics simulations, we show that in CA-SP1 tubes assembled in vitro, which represent the features of an intermediate assembly state during maturation, the SP1 peptide exists in a dynamic helix-coil equilibrium, and that the addition of the maturation inhibitors Bevirimat and DFH-055 causes stabilization of a helical form of SP1. Moreover, the maturation-arresting SP1 mutation T8I also induces helical structure in SP1 and further global dynamical and conformational changes in CA. Overall, our results show that dynamics of CA and SP1 are critical for orderly HIV-1 maturation and that small molecules can inhibit maturation by perturbing molecular motions.
Understanding the transition of brain activities towards an absence seizure, called pre-epileptic seizure, is a challenge. In this study, multiscale permutation entropy (MPE) is proposed to describe dynamical characteristics of electroencephalograph (EEG) recordings on different absence seizure states. The classification ability of the MPE measures using linear discriminant analysis is evaluated by a series of experiments. Compared to a traditional multiscale entropy method with 86.1% as its classification accuracy, the classification rate of MPE is 90.6%. Experimental results demonstrate there is a reduction of permutation entropy of EEG from the seizure-free state to the seizure state. Moreover, it is indicated that the dynamical characteristics of EEG data with MPE can identify the differences among seizure-free, pre-seizure and seizure states. This also supports the view that EEG has a detectable change prior to an absence seizure.
Spike-timing-dependent plasticity (STDP) is an important synaptic dynamics that is capable of shaping the complex spatiotemporal activity of neural circuits. In this study, we examine the effects of STDP on the spatiotemporal patterns of a spatially extended, two-dimensional spiking neural circuit. We show that STDP can promote the formation of multiple, localized spiking wave patterns or multiple spike timing sequences in a broad parameter space of the neural circuit. Furthermore, we illustrate that the formation of these dynamic patterns is due to the interaction between the dynamics of ongoing patterns in the neural circuit and STDP. This interaction is analyzed by developing a simple model able to capture its essential dynamics, which give rise to symmetry breaking. This occurs in a fundamentally self-organizing manner, without fine-tuning of the system parameters. Moreover, we find that STDP provides a synaptic mechanism to learn the paths taken by spiking waves and modulate the dynamics of their interactions, enabling them to be regulated. This regulation mechanism has error-correcting properties. Our results therefore highlight the important roles played by STDP in facilitating the formation and regulation of spiking wave patterns that may have crucial functional roles in brain information processing.
We report here on the interaction dynamics between flurbiprofen (FBP) and tryptophan (Trp) covalently linked in model dyads and in a complex of FBP with human serum albumin (HSA) probed by time-resolved fluorescence spectroscopy from the femto- to the nano-second timescales. In the dyads, a rapid (k > 10(10) s(-1)) dynamic quenching of the (1)FBP* fluorescence is followed by a slower (k > 10(9) s(-1)) quenching of the remaining (1)Trp* fluorescence. Both processes display a clear stereoselectivity; the rates are 2-3 times higher for the (R,S)-dyad. In addition, a red-shifted exciplex emission is observed, rising in the range of 100-200 ps. A similar two-step dynamic fluorescence quenching is also observed in the FBP-HSA complex, although the kinetics of the involved processes are slower. The characteristic reorientational times determined for the two enantiomeric forms of FBP in the protein show that the interaction is stronger for the ®-form. This is, to our knowledge, the first observation of stereo-selective flurbiprofen-tryptophan interaction dynamics with femtosecond time resolution.
Membrane-Proximal Ectodomain Region (MPER) of HIV-1 gp41 is known to have several epitopes of monoclonal antibodies. It also plays an important role in the membrane fusion process that is well-evidenced, though not well-elucidated. There are also disputes over the true structure of MPER. In this study, MPER NMR structure in the presence of DPC micelle is used in the molecular dynamic (MD) simulation to elucidate structural dynamics and adsorption to model MPER interaction in a membrane environment. Polarized protein-specific charge (PPC) derived from its NMR structure is found to better preserve the helical structure found in the NMR structure compared to AMBER03 calculation. The preserved helical structure also adsorb to the micelle using the hydrophobic side-chains, consistent to the NMR structure. Ab initio folding of MPER predicts a structure quite in well agreement with the NMR structure (RMSd 3.9 Å) and shows that the micelle plays a role in the folding process. Proteins 2013. © 2013 Wiley Periodicals, Inc.