Use of very long-distance NOEs in a fully deuterated protein: an approach for rapid protein fold determination

The high sensitivity of modern NMR instrumentation, in combination with full deuteration, enabled the measurement of long-range NOEs between amide protons in a fully deuterated protein corresponding to distances up to 8A. These are beyond the limit normally observed in protonated samples. Such long-distance NOEs could be observed using long mixing times, which became possible due to reduced spin diffusion and T1 relaxation of the amide protons in the fully deuterated sample. This information was used in combination with secondary structure restraints derived from secondary chemical shifts for structure calculations. With these backbone amide proton NOEs only, a unique fold could be obtained with positional root mean square deviations from the average of 1.30 and 2.25 A for backbone and heavy atoms, respectively. Despite the low density of restraints, no mirror image problems were observed. Addition of sidechain NOE information increased the precision of the ensemble and in particular of the core packing. The structures obtained in this way were close to the published crystal structure. NOE completeness analysis revealed that the cumulative completeness is still more than 80% for an 8.0 A cut-off distance.     

Rapid crack growth in a thermoelastic solid under mixed-mode thermomechanical loading

A two-dimensional steady-sate analysis of semi-infinite brittlecrack growth at a constant subcritical rate in an unboundedfully-coupled thermoelastic solid under mixed-mode thermomechanicalloading is made. The loading consists of normal and shear tractionsand heat fluxes applied as point sources (line loads in theout-of-plane direction). A related problem is solved exactly in an integral transformspace, and robust asymptotic forms used to reduce the originalproblem to a set of integral equations. The equations are partiallycoupled and exhibit operators of both Cauchy and Abel types,yet can be solved analytically. The temperature change field at a distance from the moving crackedge is then constructed, and its dominant term is found tobe controlled by the imposed heat fluxes. The role of this termis, indeed, enhanced if the heat fluxes serve to render thecrack as a net heat source/sink for the solid, as opposed tobeing a transmitter of heat across its plane. More generally,the influence of the thermoelastic coupling on this field, aswell as other functions, is found to increase with crack speed.     

Synthetic magnetic opals

We present studies of novel nanocomposites of BiNi impregnated into the structure of opals as well as inverse opals. Atomic force microscopy and high resolution elemental analyses show a highly ordered structure and uniform distribution of the BiNi filler in the matrix. These BiNi-based nanocomposites are found to exhibit distinct ferromagnetic-like ordering with transition temperature of about 675 K. As far as we know there exists no report in literature on any BiNi compound which is magnetic.     

Sampling of Glycan‐Bound Conformers by the Anti‐HIV Lectin Oscillatoria agardhii agglutinin in the Absence of Sugar

Lectins from different sources have been shown to interfere with HIV infection by binding to the sugars of viral‐envelope glycoproteins. Three‐dimensional atomic structures of a number of HIV‐inactivating lectins have been determined, both as free proteins and in glycan‐bound forms. However, details on the mechanism of recognition and binding to sugars are elusive. Herein we focus on the anti‐HIV lectin OAA from Oscillatoria agardhii: We show that in the absence of sugars in solution, both the sugar‐free and sugar‐bound protein conformations that were observed in the X‐ray crystal structures exist as conformational substates. Our results suggest that glycan recognition occurs by conformational selection within the ground state; this model differs from the popular “excited‐state” model. Our findings provide further insight into molecular recognition of the major receptor on the HIV virus by OAA. These details can potentially be used for the optimization and/or development of preventive anti‐HIV therapeutics.     

Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory

Background  

Although a large body of knowledge about both brain structure and function has been gathered over the last decades, we still have a poor understanding of their exact relationship. Graph theory provides a method to study the relation between network structure and function, and its application to neuroscientific data is an emerging research field. We investigated topological changes in large-scale functional brain networks in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) by means of graph theoretical analysis of resting-state EEG recordings. EEGs of 20 patients with mild to moderate AD, 15 FTLD patients, and 23 non-demented individuals were recorded in an eyes-closed resting-state. The synchronization likelihood (SL), a measure of functional connectivity, was calculated for each sensor pair in 0.5–4 Hz, 4–8 Hz, 8–10 Hz, 10–13 Hz, 13–30 Hz and 30–45 Hz frequency bands. The resulting connectivity matrices were converted to unweighted graphs, whose structure was characterized with several measures: mean clustering coefficient (local connectivity), characteristic path length (global connectivity) and degree correlation (network 'assortativity'). All results were normalized for network size and compared with random control networks.