Evidence of coexistence of change of caged dynamics at Tg and the dynamic transition at Td in solvated proteins

Mossbauer spectroscopy and neutron scattering measurements on proteins embedded in solvents including water and aqueous mixtures have emphasized the observation of the distinctive temperature dependence of the atomic mean square displacements, , commonly referred to as the dynamic transition at some temperature Td. At low temperatures, increases slowly, but it assume stronger temperature dependence after crossing Td, which depends on the time/frequency resolution of the spectrometer. Various authors have made connection of the dynamics of solvated proteins including the dynamic transition to that of glass-forming substances. Notwithstanding, no connection is made to the similar change of temperature dependence of obtained by quasielastic neutron scattering when crossing the glass transition temperature Tg, generally observed in inorganic, organic and polymeric glass-formers. Evidences are presented to show that such change of the temperature dependence of from neutron scattering at Tg is present in hydrated or solvated proteins, as well as in the solvents used unsurprisingly since the latter is just another organic glass-formers. The obtained by neutron scattering at not so low temperatures has contributions from the dissipation of molecules while caged by the anharmonic intermolecular potential at times before dissolution of cages by the onset of the Johari-Goldstein beta-relaxation. The universal change of at Tg of glass-formers had been rationalized by sensitivity to change in volume and entropy of the beta-relaxation, which is passed onto the dissipation of the caged molecules and its contribution to . The same rationalization applies to hydrated and solvated proteins for the observed change of at Tg.Comment: 28 pages, 10 figures, 1 Tabl

On the origin of the Boson peak in globular proteins

We study the Boson Peak phenomenology experimentally observed in globular proteins by means of elastic network models. These models are suitable for an analytic treatment in the framework of Euclidean Random Matrix theory, whose predictions can be numerically tested on real proteins structures. We find that the emergence of the Boson Peak is strictly related to an intrinsic mechanical instability of the protein, in close similarity to what is thought to happen in glasses. The biological implications of this conclusion are also discussed by focusing on a representative case study.Comment: Proceedings of the X International Workshop on Disordered Systems, Molveno (2006

Metastable Dynamics of the Hard-Sphere System

The reformulation of the mode-coupling theory (MCT) of the liquid-glass transition which incorporates the element of metastability is applied to the hard-sphere system. It is shown that the glass transition in this system is not a sharp one at the special value of the density or the packing fraction, which is in contrast to the prediction by the conventional MCT. Instead we find that the slowing down of the dynamics occurs over a range of values of the packing fraction. Consequently, the exponents governing the sequence of time relaxations in the intermediate time regime are given as functions of packing fraction with one additional parameter which describes the overall scale of the metastable potential energy for defects in the hard-sphere system. Implications of the present model on the recent experiments on colloidal systems are also discussed.Comment: 21 pages, 5 figures (available upon request), RevTEX3.0, JFI Preprint

Dissipative electro-elastic network model of protein electrostatics

We propose a dissipative electro-elastic network model (DENM) to describe the dynamics and statistics of electrostatic fluctuations at active sites of proteins. The model combines the harmonic network of residue beads with overdamped dynamics of the normal modes of the network characterized by two friction coefficients. The electrostatic component is introduced to the model through atomic charges of the protein force field. The overall effect of the electrostatic fluctuations of the network is recorded through the frequency-dependent response functions of the electrostatic potential and electric field at the active site. We also consider the dynamics of displacements of individual residues in the network and the dynamics of distances between pairs of residues. The model is tested against loss spectra of residue displacements and the electrostatic potential and electric field at the heme's iron from all-atom molecular dynamics simulations of three hydrated globular proteins

Metastable Dynamics above the Glass Transition

The element of metastability is incorporated in the fluctuating nonlinear hydrodynamic description of the mode coupling theory (MCT) of the liquid-glass transition. This is achieved through the introduction of the defect density variable $n$ into the set of slow variables with the mass density $\rho$ and the momentum density ${\bf g}$. As a first approximation, we consider the case where motions associated with $n$ are much slower than those associated with $\rho$. Self-consistently, assuming one is near a critical surface in the MCT sense, we find that the observed slowing down of the dynamics corresponds to a certain limit of a very shallow metastable well and a weak coupling between $\rho$ and $n$. The metastability parameters as well as the exponents describing the observed sequence of time relaxations are given as smooth functions of the temperature without any evidence for a special temperature. We then investigate the case where the defect dynamics is included. We find that the slowing down of the dynamics corresponds to the system arranging itself such that the kinetic coefficient $\gamma_v$ governing the diffusion of the defects approaches from above a small temperature-dependent value $\gamma^c_v$.Comment: 38 pages, 14 figures (6 figs. are included as a uuencoded tar- compressed file. The rest is available upon request.), RevTEX3.0+eps

Evaluating the effects of antimicrobial drug use on the ecology of antimicrobial resistance and microbial community structure in beef feedlot cattle

IntroductionUse of antimicrobial drugs (AMDs) in food producing animals has received increasing scrutiny because of concerns about antimicrobial resistance (AMR) that might affect consumers. Previously, investigations regarding AMR have focused largely on phenotypes of selected pathogens and indicator bacteria, such as Salmonella enterica or Escherichia coli. However, genes conferring AMR are known to be distributed and shared throughout microbial communities. The objectives of this study were to employ target-enriched metagenomic sequencing and 16S rRNA gene amplicon sequencing to investigate the effects of AMD use, in the context of other management and environmental factors, on the resistome and microbiome in beef feedlot cattle.MethodsThis study leveraged samples collected during a previous longitudinal study of cattle at beef feedlots in Canada. This included fecal samples collected from randomly selected individual cattle, as well as composite-fecal samples from randomly selected pens of cattle. All AMD use was recorded and characterized across different drug classes using animal defined daily dose (ADD) metrics.ResultsOverall, fecal resistome composition was dominated by genes conferring resistance to tetracycline and macrolide-lincosamide-streptogramin (MLS) drug classes. The diversity of bacterial phyla was greater early in the feeding period and decreased over time in the feedlot. This decrease in diversity occurred concurrently as the microbiome represented in different individuals and different pens shifted toward a similar composition dominated by Proteobacteria and Firmicutes. Some antimicrobial drug exposures in individuals and groups were associated with explaining a statistically significant proportion of the variance in the resistome, but the amount of variance explained by these important factors was very small (<0.6% variance each), and smaller than associations with other factors measured in this study such as time and feedlot ID. Time in the feedlot was associated with greater changes in the resistome for both individual animals and composite pen-floor samples, although the proportion of the variance associated with this factor was small (2.4% and 1.2%, respectively).DiscussionResults of this study are consistent with other investigations showing that, compared to other factors, AMD exposures did not have strong effects on antimicrobial resistance or the fecal microbial ecology of beef cattle

LENDA, a Low Energy Neutron Detector Array for experiments with radioactive beams in inverse kinematics

The Low Energy Neutron Detector Array (LENDA) is a neutron time-of-flight (TOF) spectrometer developed at the National Superconducting Cyclotron Lab- oratory (NSCL) for use in inverse kinematics experiments with rare isotope beams. Its design has been motivated by the need to study the spin-isospin response of unstable nuclei using (p, n) charge-exchange reactions at intermediate energies (> 100 MeV/u). It can be used, however, for any reaction study that involves emission of low energy neutrons (150 keV - 10 MeV). The array consists of 24 plastic scintillator bars and is capable of registering the recoiling neutron energy and angle with high detection efficiency. The neutron energy is determined by the time-of-flight technique, while the position of interaction is deduced using the timing and energy information from the two photomultipliers of each bar. A simple test setup utilizing radioactive sources has been used to characterize the array. Results of test measurements are compared with simulations. A neutron energy threshold of < 150 keV, an intrinsic time (position) resolution of \sim 400 ps (\sim 6 cm) and an efficiency > 20 % for neutrons below 4 MeV have been obtained.Comment: Version accepted for publication in Nucl. Instr. Methods A. Revised text, 2 new figures added (one in section 4 and one in section 7

Can Molecular Motors Drive Distance Measurements in Injured Neurons?

Injury to nerve axons induces diverse responses in neuronal cell bodies, some of which are influenced by the distance from the site of injury. This suggests that neurons have the capacity to estimate the distance of the injury site from their cell body. Recent work has shown that the molecular motor dynein transports importin-mediated retrograde signaling complexes from axonal lesion sites to cell bodies, raising the question whether dynein-based mechanisms enable axonal distance estimations in injured neurons? We used computer simulations to examine mechanisms that may provide nerve cells with dynein-dependent distance assessment capabilities. A multiple-signals model was postulated based on the time delay between the arrival of two or more signals produced at the site of injury–a rapid signal carried by action potentials or similar mechanisms and slower signals carried by dynein. The time delay between the arrivals of these two types of signals should reflect the distance traversed, and simulations of this model show that it can indeed provide a basis for distance measurements in the context of nerve injuries. The analyses indicate that the suggested mechanism can allow nerve cells to discriminate between distances differing by 10% or more of their total axon length, and suggest that dynein-based retrograde signaling in neurons can be utilized for this purpose over different scales of nerves and organisms. Moreover, such a mechanism might also function in synapse to nucleus signaling in uninjured neurons. This could potentially allow a neuron to dynamically sense the relative lengths of its processes on an ongoing basis, enabling appropriate metabolic output from cell body to processes

Low-Temperature Polymorphic Phase Transition in a Crystalline Tripeptide L-Ala-L-Pro-Gly·H2O Revealed by Adiabatic Calorimetry

We demonstrate application of precise adiabatic vacuum calorimetry to observation of phase transition in the tripeptide l-alanyl-l-prolyl-glycine monohydrate (APG) from 6 to 320 K and report the standard thermodynamic properties of the tripeptide in the entire range. Thus, the heat capacity of APG was measured by adiabatic vacuum calorimetry in the above temperature range. The tripeptide exhibits a reversible first-order solid-to-solid phase transition characterized by strong thermal hysteresis. We report the standard thermodynamic characteristics of this transition and show that differential scanning calorimetry can reliably characterize the observed phase transition with <5 mg of the sample. Additionally, the standard entropy of formation from the elemental substances and the standard entropy of hypothetical reaction of synthesis from the amino acids at 298.15 K were calculated for the studied tripeptide.National Institute of Biomedical Imaging and Bioengineering (U.S.) (EB-003151)National Institute of Biomedical Imaging and Bioengineering (U.S.) (EB-001960)National Institute of Biomedical Imaging and Bioengineering (U.S.) (EB-002026