Functional Bacterial Amyloids: Understanding Fibrillation,Regulating Biofilm Fibril Formation and Organizing Surface Assemblies

Functional amyloid is produced by many organisms but is particularly well understood in bacteria, where proteins such as CsgA (E. coli) and FapC (Pseudomonas) are assembled as functional bacterial amyloid (FuBA) on the cell surface in a carefully optimized process. Besides a host of helper proteins, FuBA formation is aided by multiple imperfect repeats which stabilize amyloid and streamline the aggregation mechanism to a fast-track assembly dominated by primary nucleation. These repeats, which are found in variable numbers in Pseudomonas, are most likely the structural core of the fibrils, though we still lack experimental data to determine whether the repeats give rise to β-helix structures via stacked β-hairpins (highly likely for CsgA) or more complicated arrangements (possibly the case for FapC). The response of FuBA fibrillation to denaturants suggests that nucleation and elongation involve equal amounts of folding, but protein chaperones preferentially target nucleation for effective inhibition. Smart peptides can be designed based on these imperfect repeats and modified with various flanking sequences to divert aggregation to less stable structures, leading to a reduction in biofilm formation. Small molecules such as EGCG can also divert FuBA to less organized structures, such as partially-folded oligomeric species, with the same detrimental effect on biofilm. Finally, the strong tendency of FuBA to self-assemble can lead to the formation of very regular two-dimensional amyloid films on structured surfaces such as graphite, which strongly implies future use in biosensors or other nanobiomaterials. In summary, the properties of functional amyloid are a much-needed corrective to the unfortunate association of amyloid with neurodegenerative disease and a testimony to nature’s ability to get the best out of a protein fold.     

Thermodynamic equilibrium between locally excited and charge-transfer states through thermally activated charge transfer in 1-(pyren-2′-yl)-o-carborane

Reversible conversion between excited-states plays an important role in many photophysical phenomena. Using 1-(pyren-2′-yl)-o-carborane as a model, we studied the photoinduced reversible charge-transfer (CT) process and the thermodynamic equilibrium between the locally-excited (LE) state and CT state, by combining steady state, time-resolved, and temperature-dependent fluorescence spectroscopy, fs- and ns-transient absorption, and DFT and LR-TDDFT calculations. Our results show that the energy gaps and energy barriers between the LE, CT, and a non-emissive ‘mixed’ state of 1-(pyren-2′-yl)-o-carborane are very small, and all three excited states are accessible at room temperature. The internal-conversion and reverse internal-conversion between LE and CT states are significantly faster than the radiative decay, and the two states have the same lifetimes and are in thermodynamic equilibrium.

Reversible conversion between excited-states is key to many photophysical phenomena. We studied the equilibrium between LE and CT states by time-resolved and temperature-dependent fluorescence, fs- and ns-transient absorption, and LR-TDDFT calculations.     

The Morphology of Liquid-Crystalline Polymers and the Possible Consequences for their Rheological Behaviour

Abstract

Polymer liquid crystals can occur as polydomain materials where the domain size may be tens of microns. While the material within each domain may be characterized by a common order parameter, the directors of the domains can be more or less randomly distributed. Since the transition from polydomain to monodomain material only involves the removal of grain boundaries and the alignment of directors, the free energy change must necessarily be small. Such a transition can readily be achieved, therefore, by the action of any external field: electrical, magnetic, stress or surface. In this work optical photomicrographs of polymeric liquid crystals with widely varying and in some cases well controlled morphologies are presented. Probable dependence of rheological behaviour on morphology is also discussed. Such dependence is expected to be considerable under certain conditions. Due to experimental and sample limitations, however, direct correlations of rheology and morphology are sparse. Morphological consequences for the rheology of liquid-crystalline materials can be exemplified by the following possibilities. In contrast to the case of isotropic melts, wall effects can be non-negligible. Zero shear rate rheological parameters are not expected to be uniquely defined quantities since the domain sizes are large and the director may not be effectively averaged over typical sample dimensions. Non-zero shear-rate measurements of rheological parameters is effected by the propensity of: (1) individual domain directors to align under the influence of a stress field and (2) flow alignment to dominate surface-induced alignment above some critical shear rate. The effects might be manifested by a non-newtonian regime as well as yield stress behaviour and thixotropy. The kinetics of relaxation from mono- to poly-domain material has implications for the dynamic response and rheological hysterises of the material.     

Spectral estimation for characterization of acoustic aberration

Spectral estimation based on acoustic backscatter from a motionless stochastic medium is described for characterization of aberration in ultrasonic imaging. The underlying assumptions for the estimation are: The correlation length of the medium is short compared to the length of the transmitted acoustic pulse, an isoplanatic region of sufficient size exists around the focal point, and the backscatter can be modeled as an ergodic stochastic process. The motivation for this work is ultrasonic imaging with aberration correction. Measurements were performed using a two-dimensional array system with 80 x 80 transducer elements and an element pitch of 0.6 mm. The f number for the measurements was 1.2 and the center frequency was 3.0 MHz with a 53% bandwidth. Relative phase of aberration was extracted from estimated cross spectra using a robust least-mean-square-error method based on an orthogonal expansion of the phase differences of neighboring wave forms as a function of frequency. Estimates of cross-spectrum phase from measurements of random scattering through a tissue-mimicking aberrator have confidence bands approximately +/- 5 degrees wide. Both phase and magnitude are in good agreement with a reference characterization obtained from a point scatterer.     

One-dimensional non-relativistic and relativistic Brownian motions: a microscopic collision model

We study a simple microscopic model for the one-dimensional stochastic motion of a (non-)relativistic Brownian particle, embedded into a heat bath consisting of (non-)relativistic particles. The stationary momentum distributions are identified self-consistently (for both Brownian and heat bath particles) by means of two coupled integral criteria. The latter follow directly from the kinematic conservation laws for the microscopic collision processes, provided one additionally assumes probabilistic independence of the initial momenta. It is shown that, in the non-relativistic case, the integral criteria do correctly identify the Maxwellian momentum distributions as stationary (invariant) solutions. Subsequently, we apply the same criteria to the relativistic case. Surprisingly, we find here that the stationary momentum distributions differ slightly from the standard Jüttner distribution by an additional prefactor proportional to the inverse relativistic kinetic energy.     

Anomalous temperature dependence of elastic constant c44 in V, Nb, Ta, Pd, and Pt

The anomalous temperature dependence of elastic constant c₄₄ for elements V, Nb, Ta, Pd, and Pt, has been calculated using first-principles theory. It is shown that the variation of elastic constant for simple elements can be approximated as the sum of thermal expansion and electronic components. The thermal expansion contributes the normal linearly decreasing effect to the elastic constant with temperature, while electronic contribution is determined by the unique character of electronic structure of elements and leads to the anomalous effect to the elastic constant with temperature.     

Changes in intratumor heterogeneity in blood perfusion in intradermal human melanoma xenografts during tumor growth assessed by DCE-MRI

The purpose of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to search for systematic intratumor heterogeneity in blood perfusion in human melanoma xenografts growing intradermally in BALB/c-nu/nu mice. Six xenografted tumors of an amelanotic human melanoma line (A-07) were included in the study. DCE-MRI was performed daily for 5 days by using spoiled-gradient recalled sequences. Tumor images of E.F (E is initial extraction fraction and F is perfusion) were produced by subjecting DCE-MRI data to Kety analysis. E.F was used as a measure of tumor blood perfusion, since comparative studies have shown that E.F is closely related to blood perfusion in A-07 tumors. The E.F images indicated that the intratumor heterogeneity in blood perfusion was similar in all investigated tumors. The blood perfusion was low in the center of the tumors and increased toward the tumor periphery in the dorsal and ventral direction by a factor of 3-4, but not in the lateral and medial direction. The magnitude of the heterogeneity increased by a factor of approximately 2 during tumor growth. In conclusion, intradermal human melanoma xenografts show significant systematic intratumor heterogeneity in blood perfusion.     

The Aharonov–Bohm effect in graphene rings

This is a review of electronic quantum interference in mesoscopic ring structures based on graphene, with a focus on the interplay between the Aharonov–Bohm effect and the peculiar electronic and transport properties of this material. We first present an overview on recent developments of this topic, both from the experimental as well as the theoretical side. We then review our recent work on signatures of two prominent graphene-specific features in the Aharonov–Bohm conductance oscillations, namely Klein tunneling and specular Andreev reflection. We close with an assessment of experimental and theoretical development in the field and highlight open questions as well as potential directions of the developments in future work.