The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding.

One of the most exciting developments in the field of biological physics in recent years is the ability to manipulate single molecules and probe their properties and function. Since its emergence over two decades ago, single molecule force spectroscopy has become a powerful tool to explore the response of biological molecules, including proteins, DNA, RNA and their complexes, to the application of an applied force. The force versus extension response of molecules can provide valuable insight into its mechanical stability, as well as details of the underlying energy landscape. In this review we will introduce the technique of single molecule force spectroscopy using the atomic force microscope (AFM), with particular focus on its application to study proteins. We will review the models which have been developed and employed to extract information from single molecule force spectroscopy experiments. Finally, we will end with a discussion of future directions in this field

The Role of Cardiovascular Magnetic Resonance in Pediatric Congenital Heart Disease

Cardiovascular magnetic resonance (CMR) has expanded its role in the diagnosis and management of congenital heart disease (CHD) and acquired heart disease in pediatric patients. Ongoing technological advancements in both data acquisition and data presentation have enabled CMR to be integrated into clinical practice with increasing understanding of the advantages and limitations of the technique by pediatric cardiologists and congenital heart surgeons. Importantly, the combination of exquisite 3D anatomy with physiological data enables CMR to provide a unique perspective for the management of many patients with CHD. Imaging small children with CHD is challenging, and in this article we will review the technical adjustments, imaging protocols and application of CMR in the pediatric population

Evidence and modeling of turbulence bifurcation in L-mode confinement transitions on Alcator C-Mod

© 2020 Author(s). Analysis and modeling of rotation reversal hysteresis experiments show that a single turbulent bifurcation is responsible for the Linear to Saturated Ohmic Confinement (LOC/SOC) transition and concomitant intrinsic rotation reversal on Alcator C-Mod. Plasmas on either side of the reversal exhibit different toroidal rotation profiles and therefore different turbulence characteristics despite the profiles of density and temperature, which are indistinguishable within measurement uncertainty. Elements of this bifurcation are also shown to persist for auxiliary heated L-modes. The deactivation of subdominant (in the linear growth rate and contribution to heat transport) ion temperature gradient and trapped electron mode instabilities is identified as the only possible change in turbulence within a reduced quasilinear transport model across the reversal, which is consistent with the measured profiles and inferred heat and particle fluxes. Experimental constraints on a possible change from strong to weak turbulence, outside the description of the quasilinear model, are also discussed. These results indicate an explanation for the LOC/SOC transition that provides a mechanism for the hysteresis through the dynamics of subdominant modes and changes in their relative populations and does not involve a change in the most linearly unstable ion-scale drift-wave instability

Novel modes of rhythmic burst firing at cognitively-relevant frequencies in thalamocortical neurons.

It is now widely accepted that certain types of cognitive functions are intimately related to synchronized neuronal oscillations at both low (alpha/theta) (4-7/8-13 Hz) and high (beta/gamma) (18-35/30-70 Hz) frequencies. The thalamus is a key participant in many of these oscillations, yet the cellular mechanisms by which this participation occurs are poorly understood. Here we describe how, under appropriate conditions, thalamocortical (TC) neurons from different nuclei can exhibit a wide array of largely unrecognised intrinsic oscillatory activities at a range of cognitively-relevant frequencies. For example, both metabotropic glutamate receptor (mGluR) and muscarinic Ach receptor (mAchR) activation can cause rhythmic bursting at alpha/theta frequencies. Interestingly, key differences exist between mGluR- and mAchR-induced bursting, with the former involving extensive dendritic Ca2+ electrogenesis and being mimicked by a non-specific block of K+ channels with Ba2+, whereas the latter appears to be more reliant on proximal Na+ channels and a prominent spike afterdepolarization (ADP). This likely relates to the differential somatodendritic distribution of mGluRs and mAChRs and may have important functional consequences. We also show here that in similarity to some neocortical neurons, inhibiting large-conductance Ca2+-activated K+ channels in TC neurons can lead to fast rhythmic bursting (FRB) at approximately 40 Hz. This activity also appears to rely on a Na+ channel-dependent spike ADP and may occur in vivo during natural wakefulness. Taken together, these results show that TC neurons are considerably more flexible than generally thought and strongly endorse a role for the thalamus in promoting a range of cognitively-relevant brain rhythms

Accurate computation of quaternions from rotation matrices

The final publication is available at link.springer.comThe main non-singular alternative to 3×3 proper orthogonal matrices, for representing rotations in R3, is quaternions. Thus, it is important to have reliable methods to pass from one representation to the other. While passing from a quaternion to the corresponding rotation matrix is given by Euler-Rodrigues formula, the other way round can be performed in many different ways. Although all of them are algebraically equivalent, their numerical behavior can be quite different. In 1978, Shepperd proposed a method for computing the quaternion corresponding to a rotation matrix which is considered the most reliable method to date. Shepperd’s method, thanks to a voting scheme between four possible solutions, always works far from formulation singularities. In this paper, we propose a new method which outperforms Shepperd’s method without increasing the computational cost.Peer ReviewedPostprint (author's final draft

Platinum-group element and Au geochemistry of Late Archean to Proterozoic calc-alkaline and alkaline magmas in the Yilgarn Craton, Western Australia

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe Yilgarn Craton of Western Australia is one of the largest Archean cratons in the world and is well-known for its metal endowment. In order to provide new insights into its metallogenic fertility and the nature of the upper mantle that lies underneath the craton, this study investigates the poorly constrained platinum-group element (PGE) and gold signatures of a selected suite of calc-alkaline lamprophyres, ultramafic lamprophyres, carbonatites and orangeites, ranging in age from the Proterozoic to the Late Archean. Proterozoic ultramafic lamprophyres and carbonatites within the Eastern Goldfields Superterrane (EGS) of the Yilgarn Craton have anomalously low PGE contents (Ir = 0.1–1.3 ppb; Ru = < 0.08 to 3.6 ppb; Rh = <0.04 to 0.4 ppb; Pt = <0.17 to 3.3 ppb; Pd = <0.12 to 4.4 ppb) and variable Au contents (<0.4 to 9.8 ppb). Based on their low PGE contents and unfractionated PGE patterns with (Pd/Ir)N ratios up to ~6, it is suggested that these magmas may derive from extremely low-degree partial melting of the convective mantle. Conversely, the Late Archean calc-alkaline lamprophyres in the EGS exhibit comparatively fractionated PGE patterns with (Pd/Ir)N ratios up to ~27 and variable Au concentrations, including localised anomalous enrichments (up to 13.8 ppb). The fractionated PGE patterns are explained by incongruent melting of mantle sulfides with potential contribution from PPGE- and Au-bearing alloys, which would preferentially contribute Pt, Pd and Au over Ir, Ru and Rh. Combination of elevated Au and volatile contents in these rocks is consistent with derivation from a mantle source that was metasomatised by slab-derived fluids along a laterally extensive Late Archean subduction setting. This process may have provided a first-order control on the exceptional gold endowment of the Eastern Goldfields Superterrane.Australian Government Research Training ProgramAustralian Research Council (ARC)Minerals Research Institute of Western Australi

Effects of hydroxyapatite and PDGF concentrations on osteoblast growth in a nanohydroxyapatite-polylactic acid composite for guided tissue regeneration

The technique of guided tissue regeneration (GTR) has evolved over recent years in an attempt to achieve periodontal tissue regeneration by the use of a barrier membrane. However, there are significant limitations in the currently available membranes and overall outcomes may be limited. A degradable composite material was investigated as a potential GTR membrane material. Polylactic acid (PLA) and nanohydroxyapatite (nHA) composite was analysed, its bioactive potential and suitability as a carrier system for growth factors were assessed. The effect of nHA concentrations and the addition of platelet derived growth factor (PDGF) on osteoblast proliferation and differentiation was investigated. The bioactivity was dependent on the nHA concentration in the films, with more apatite deposited on films containing higher nHA content. Osteoblasts proliferated well on samples containing low nHA content and differentiated on films with higher nHA content. The composite films were able to deliver PDGF and cell proliferation increased on samples that were pre absorbed with the growth factor. nHA–PLA composite films are able to deliver active PDGF. In addition the bioactivity and cell differentiation was higher on films containing more nHA. The use of a nHA–PLA composite material containing a high concentration of nHA may be a useful material for GTR membrane as it will not only act as a barrier, but may also be able to enhance bone regeneration by delivery of biologically active molecules

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential