Three-dimensional elemental bio-imaging of Fe, Zn, Cu, Mn and P in a 6-hydroxydopamine lesioned mouse brain

Three dimensional maps of iron (Fe), zinc (Zn), copper (Cu), manganese (Mn) and phosphorous (P) in a 6-hydroxydopamine (6-OHDA) lesioned mouse brain were constructed employing a novel quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method known as elemental bio-imaging. The 3D maps were produced by ablating serial consecutive sections taken from the same animal. Each section was quantified against tissue standards resulting in a three dimensional map that represents the variation of trace element concentrations of the mouse brain in the area surrounding the substantia nigra (SN). Damage caused by the needle or the toxin did not alter the distribution of Zn, and Cu but significantly altered Fe in and around the SN and both Mn and Fe around the needle track. A 20% increase in nigral Fe concentration was observed within the lesioned hemisphere. This technique clearly shows the natural heterogeneous distributions of these elements throughout the brain and the perturbations that occur following trauma or intoxication. The method may applied to three-dimensional modelling of trace elements in a wide range of tissue samples. © 2010 The Royal Society of Chemistry

Quantitative elemental bio-imaging of Mn, Fe, Cu and Zn in 6-hydroxydopamine induced Parkinsonism mouse models

This study demonstrates the application of quantitative elemental bio-imaging for the determination of the distribution Cu, Mn, Fe and Zn in Parkinsonism mouse model brains. Elevated concentrations of these metals within the substantia nigra (SN) are suspected to play a role on the development of Parkinson's disease. Elemental bio-imaging employs laser ablation inductively coupled mass spectrometry (LA-ICP-MS) to construct images of trace element distribution. Quantitative data was produced by ablating the standard tissue sections and recording the mean signal intensity calibrated against multi level matrix matched tissue standards. The concentrations of Fe within the substantia nigra of the lesioned animals increased significantly when compared against control animals. Furthermore, the data was compared against solution nebulisation ICP-MS in which the whole substantia nigra was excised. The trends were the same for both methods; however the elemental bio-imaging method returned significantly higher concentrations. This was caused by dilution from inclusion of surrounding tissue of the SN during the excision procedure. © The Royal Society of Chemistry 2009

Imaging and controlling electron transport inside a quantum ring

Traditionally, the understanding of quantum transport, coherent and ballistic1, relies on the measurement of macroscopic properties such as the conductance. While powerful when coupled to statistical theories, this approach cannot provide a detailed image of "how electrons behave down there". Ideally, understanding transport at the nanoscale would require tracking each electron inside the nano-device. Significant progress towards this goal was obtained by combining Scanning Probe Microscopy (SPM) with transport measurements2-7. Some studies even showed signatures of quantum transport in the surrounding of nanostructures4-6. Here, SPM is used to probe electron propagation inside an open quantum ring exhibiting the archetype of electron wave interference phenomena: the Aharonov-Bohm effect8. Conductance maps recorded while scanning the biased tip of a cryogenic atomic force microscope above the quantum ring show that the propagation of electrons, both coherent and ballistic, can be investigated in situ, and even be controlled by tuning the tip potential.Comment: 11 text pages + 3 figure

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Association between reduced bronchodilatory effect of deep inspiration and loss of alveolar attachments

BACKGROUND: We have previously shown that the bronchodilatory effect of deep inspiration is attenuated in individuals with COPD. This study was designed to investigate whether the impairment in this effect is associated with loss of alveolar attachments. METHODS: We measured deep inspiration (DI)-induced bronchodilation in 15 individuals with and without COPD (67 ± 2.2 yrs of age, mean ± SEM) undergoing lobar resection for peripheral pulmonary nodule. Prior to surgery, we measured TLCO and determined the bronchodilatory effect of deep inspiration after constricting the airways with methacholine. The number of destroyed alveolar attachments, as well as airway wall area and airway smooth muscle area, were determined in tumor-free, peripheral lung tissue. RESULTS: The bronchodilatory effect of deep inspiration correlated inversely with the % destroyed attachments (r = -0.51, p = 0.05) and directly with the airway smooth muscle area (r = 0.59, p = 0.03), but not with the total wall area (r = 0.39, p = 0.15). CONCLUSION: We postulate that attenuation of airway stretch due to loss of alveolar attachments contributes to the loss of the bronchodilatory effect of lung inflation in COPD

On the relationship between the reversed hazard rate and elasticity

Despite hazard and reversed hazard rates sharing a number of similar aspects, reversed hazard functions are far less frequently used. Understanding their meaning is not a simple task. The aim of this paper is to expand the usefulness of the reversed hazard function by relating it to other well-known concepts broadly used in economics: (linear or cumulative) rates of increase and elasticity. This will make it possible (i) to improve our understanding of the consequences of using a particular distribution and, in certain cases, (ii) to introduce our hypotheses and knowledge about the random process in a more meaningful and intuitive way, thus providing a means to achieving distributions that would otherwise be hardly imaginable or justifiable

Correction to: The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease.

Following publication of the original article [1], the author identified an error in Fig. 4E. The data and statistics were correct, but the synaptophysin blot was incorrect. The incorrect (Fig. 1) and correct figure (Fig. 2) are shown in this correction article. (Figure presented.)