Dried Protein Structure Revealed at the Residue Level by Liquid-Observed Vapor Exchange NMR

Water is key to protein structure and stability, yet the relationship between protein-water interactions and structure is poorly understood, in part because there are few techniques that permit the study of dehydrated protein structure at high resolution. Here, we describe liquid-observed vapor exchange (LOVE) NMR, a solution NMR-based method that provides residue-level information about the structure of dehydrated proteins. Using the model protein GB1, we show that LOVE NMR measurements reflect the fraction of the dried protein population trapped in a conformation where a given residue is protected from exchange with D2O vapor. Comparisons to solution hydrogen-deuterium exchange data affirm that the dried protein structure is strongly influenced by local solution stability and that the mechanism of dehydration protection exerted by the widely used protectant trehalose differs from its mechanism of stabilization in solution. Our results highlight the need for refined models of cosolute-mediated dehydration protection and demonstrate the ability of LOVE NMR to inform such models

The falling chain of Hopkins, Tait, Steele and Cayley

A uniform, flexible and frictionless chain falling link by link from a heap by the edge of a table falls with an acceleration $g/3$ if the motion is nonconservative, but $g/2$ if the motion is conservative, $g$ being the acceleration due to gravity. Unable to construct such a falling chain, we use instead higher-dimensional versions of it. A home camcorder is used to measure the fall of a three-dimensional version called an $xyz$-slider. After frictional effects are corrected for, its vertical falling acceleration is found to be $a_x/g = 0.328 \pm 0.004$. This result agrees with the theoretical value of $a_x/g = 1/3$ for an ideal energy-conserving $xyz$-slider.Comment: 17 pages, 5 figure

Measurements of dense fuel hydrodynamics in the NIF burning plasma experiments using backscattered neutron spectroscopy

The hydrodynamics of the dense confining fuel shell is of great importance in defining the behaviour of the burning plasma and burn propagation regimes of inertial confinement fusion experiments. However, it is difficult to probe due to its low emissivity in comparison to the central fusion core. In this work, we utilise the backscattered neutron spectroscopy technique to directly measure the hydrodynamic conditions of the dense fuel during fusion burn. Experimental data is fit to obtain dense fuel velocities and apparent ion temperatures. Trends of these inferred parameters with yield and velocity of the burning plasma are used to investigate their dependence on alpha heating and low mode drive asymmetry. It is shown that the dense fuel layer has an increased outward radial velocity as yield increases showing burn has continued into re-expansion, a key signature of hotspot ignition. Comparison with analytic and simulation models show that the observed dense fuel parameters are displaying signatures of burn propagation into the dense fuel layer, including a rapid increase in dense fuel apparent ion temperature with neutron yield

Using zebrafish larval models to study brain injury, locomotor and neuroinflammatory outcomes following intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) is a devastating condition with limited treatment options, and current understanding of pathophysiology is incomplete. Spontaneous cerebral bleeding is a characteristic of the human condition that has proven difficult to recapitulate in existing pre-clinical rodent models. Zebrafish larvae are frequently used as vertebrate disease models and are associated with several advantages, including high fecundity, optical translucency and non-protected status prior to 5 days post-fertilisation. Furthermore, other groups have shown that zebrafish larvae can exhibit spontaneous ICH. The aim of this study was to investigate whether such models can be utilised to study the pathological consequences of bleeding in the brain, in the context of pre-clinical ICH research. Here, we compared existing genetic (bubblehead) and chemically inducible (atorvastatin) zebrafish larval models of spontaneous ICH and studied the subsequent disease processes. Through live, non-invasive imaging of transgenic fluorescent reporter lines and behavioural assessment we quantified brain injury, locomotor function and neuroinflammation following ICH. We show that ICH in both zebrafish larval models is comparable in timing, frequency and location. ICH results in increased brain cell death and a persistent locomotor deficit. Additionally, in haemorrhaged larvae we observed a significant increase in macrophage recruitment to the site of injury. Live in vivo imaging allowed us to track active macrophage-based phagocytosis of dying brain cells 24 hours after haemorrhage. Morphological analyses and quantification indicated that an increase in overall macrophage activation occurs in the haemorrhaged brain. Our study shows that in zebrafish larvae, bleeding in the brain induces quantifiable phenotypic outcomes that mimic key features of human ICH. We hope that this methodology will enable the pre-clinical ICH community to adopt the zebrafish larval model as an alternative to rodents, supporting future high throughput drug screening and as a complementary approach to elucidating crucial mechanisms associated with ICH pathophysiology

Investigating radiatively driven, magnetized plasmas with a university scale pulsed-power generator

We present first results from a novel experimental platform which is able to access physics relevant to topics including indirect-drive magnetised ICF; laser energy deposition; various topics in atomic physics; and laboratory astrophysics (for example the penetration of B-fields into HED plasmas). This platform uses the X-Rays from a wire array Z-Pinch to irradiate a silicon target, producing an outflow of ablated plasma. The ablated plasma expands into ambient, dynamically significant B-fields (~5 T) which are supported by the current flowing through the Z-Pinch. The outflows have a well-defined (quasi-1D) morphology, enabling the study of fundamental processes typically only available in more complex, integrated schemes. Experiments were fielded on the MAGPIE pulsed-power generator (1.4 MA, 240 ns rise time). On this machine a wire array Z-Pinch produces an X-Ray pulse carrying a total energy of ~15 kJ over ~30 ns. This equates to an average brightness temperature of around 10 eV on-target

Function of specialized regulatory proteins and signaling pathways in exercise-induced muscle mitochondrial biogenesis

AbstractSkeletal muscle mitochondrial content and function are regulated by a number of specialized molecular pathways that remain to be fully defined. Although a number of proteins have been identified to be important for the maintenance of mitochondria in quiescent muscle, the requirement for these appears to decrease with the activation of multiple overlapping signaling events that are triggered by exercise. This makes exercise a valuable therapeutic tool for the treatment of mitochondrially based metabolic disorders. In this review, we summarize some of the traditional and more recently appreciated pathways that are involved in mitochondrial biogenesis in muscle, particularly during exercise