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Abstract: The hallmark of neurodegenerative disease in humans, including Alzheimer’s, Amyotrophic Lateral Sclerosis and Parkinson’s, lies in our inability to efficiently restore damaged neurons. Contrary to widespread belief, humans can regenerate neurons within the Peripheral Nervous System (PNS) and some areas of the Central Nervous System (CNS), however the underlying mechanisms which drive or repress complete functional and structural neuronal regeneration remain elusive. To develop our understanding of this natural phenomenon one should focus on species which are capable of efficient neuronal regeneration following neurotrauma. The earthworm species Eisenia fetida can regenerate their Cerebral Ganglion (CG) - loosely defined as the brain, within a few weeks following surgical removal. The characterization of fundamental aspects of neuronal regeneration in the earthworm promises to provide an insight as to why humans have largely lost that capability. Here we present a detailed micro-dissection protocol that has been developed to excise the CG and study the progression of its regeneration. The Ventral Nerve Cord (VNC) of the worm is a tissue which connects the CG to the rest of the nervous system via the Circumpharyngeal Connectives (CC). Exploration of molecular dynamics through changes in the transcriptome were determined in the VNC and CC at 1 week and 5-week post-decerebration using an RNAseq approach (90 million reads/condition, 100bp Paired End). RNAseq established that specific groups of genes are up- or downregulated in the regenerating VNC. More than 500 significantly enriched biological processes were identified throughout the regeneration process, including vascular development, neurogenesis and extracellular matrix organization, as well as more than 100 significantly enriched molecular functions, including calcium ion binding, metal ion binding and metalloendopeptidase activity. Differential expression of transcripts was confirmed via qPCR. Examples of transcripts which have been validated at 1w post-decerebration, include catalase (~34-fold), superoxide dismutase 1 (sod-1) (~12-fold) and transcription factor jun-B (junb) (~3-fold). On the other hand, examples of transcripts which have been validated at 5w post-decerebration, include Glial Fibrillary Acidic Protein (GFAP) (~101-fold), adam19 (~17-fold) and Bone Morphogenetic Protein 1 (BMP1) (~3-fold). Moreover, the large number of differentially expressed metalloproteins (ADAMs, BMPs, MMPs, metallothionein) identified in the transcriptome, led to the hypothesis that metal trafficking could play a role in the course of regeneration. This was confirmed using a synchrotron-based approach, namely X-Ray Fluorescence (XRF) spectroscopy, where Zinc (Zn) and Iron (Fe) show a differential distribution pattern across different stages (at 1 week to 10-weeks post-decerebration) of regeneration. Lastly, various histological techniques were implemented to characterize/describe neuronal structures during the regenerating process, including immunohistochemistry and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL). Furthermore, numerous novel markers and biological processes have been identified which, to date, have not been linked to neuronal regeneration. In summary, the results suggest that the increase of axon growth promoting factors as well the decrease of growth inhibitory factors act in conjunction to ensure efficient neuronal regeneration in the earthworm.

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Abstract: The ability to manipulate the composition of semiconductor alloys on-demand and at nanometer-scale resolutions is a powerful tool that could be exploited to tune key properties such as the electronic bandgap, mobility, and refractive index. However, existing methods to modify the composition involve altering the stoichiometry by temporal or spatial modulation of the process parameters during material growth, limiting the scalability and flexibility for device fabrication. Here, we report a laser processing method for localized tailoring of the composition in amorphous silicon-germanium (a-SiGe) nanoscale thin films on silicon substrates, post-deposition, by controlling phase segregation through the scan speed of the laser-induced molten zone. Laser-driven phase segregation at speeds adjustable from 0.1 to 100 mm s-1 allows access to previously unexplored solidification dynamics. The steady-state spatial distribution of the alloy constituents can be tuned directly by setting the constant laser scan speed to achieve indefinitely long Si1-xGex microstructures exhibiting the full range of compositions (0

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Abstract: From oxic atmosphere to metallic core, the Earth's components are broadly stratified with respect to oxygen fugacity. A simple picture of reducing oxygen fugacity with depth may be disrupted by the accumulation of oxidised crustal material in the deep lower mantle, entrained there as a result of subduction. While hotspot volcanoes are fed by regions of the mantle likely to have incorporated such recycled material, the oxygen fugacity of erupted hotspot basalts had long been considered comparable to or slightly more oxidised than that of mid-ocean ridge basalt (MORB) and more reduced than subduction zone basalts. Here we report measurements of the redox state of glassy crystal-hosted melt inclusions from tephra and quenched lava samples from the Canary and Cape Verde Islands, that we can independently show were entrapped prior to extensive sulphur degassing. We find high ferric iron to total iron ratios (Fe3+/∑Fe) of up to 0.27–0.30, indicating that mantle plume primary melts are significantly more oxidised than those associated with mid-ocean ridges and even subduction zone. These results, together with previous investigations from the Erebus, Hawaiian and Icelandic hotspots, confirm that mantle upwelling provides a return flow from the deep Earth for components of oxidised subducted lithosphere and suggest that highly oxidised material accumulates or is generated in the lower mantle. The oxidation state of the Earth's interior must therefore be highly heterogeneous and potentially locally inversely stratified.

Open Access

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Abstract: Microcalcifications are important diagnostic indicators of disease in breast tissue. Tissue microenvironments differ in many aspects between normal and cancerous cells, notably extracellular pH and glycolytic respiration. Hydroxyapatite microcalcification microstructure is also found to differ between tissue pathologies, including differential ion substitutions and the presence of additional crystallographic phases. Distinguishing between tissue pathologies at an early stage is essential to improve patient experience and diagnostic accuracy, leading to better disease outcome. This study explores the hypothesis that microenvironment features may become immortalised within calcification crystallite characteristics thus becoming indicators of tissue pathology. In total, 55 breast calcifications incorporating 3 tissue pathologies (benign – B2, ductal carcinoma in-situ - B5a and invasive malignancy - B5b) from archive formalin-fixed paraffin-embedded core needle breast biopsies were analysed using X-ray diffraction. Crystallite size and strain were determined from 548 diffractograms using Williamson-Hall analysis. There was an increased crystallinity of hydroxyapatite with tissue malignancy compared to benign tissue. Coherence length was significantly correlated with pathology grade in all basis crystallographic directions (P < 0.01), with a greater difference between benign and in situ disease compared to in-situ disease and invasive malignancy. Crystallite size and non-uniform strain contributed to peak broadening in all three pathologies. Furthermore, crystallite size and non-uniform strain normal to the basal planes increased significantly with malignancy (P < 0.05). Our findings support the view that tissue microenvironments can influence differing formation mechanisms of hydroxyapatite through acidic precursors, leading to differential substitution of carbonate into the hydroxide and phosphate sites, causing significant changes in crystallite size and non-uniform strain.

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Abstract: We present a simple two step process for the fabrication of single crystal germanium core optical fibers. The core material is deposited into a capillary in a highly polycrystalline state using the pressure assisted filling technique. The cores are then melted and recrystallized in single crystal form using a scanning CO2 laser process. This technique is far quicker than the high pressure chemical deposition technique and overcomes all of the oxygen in-diffusion issues associated with the molten core drawing technique. We produce small core fiber 1 lm radii and length in the cm regime. It is anticipated that this process can be be optimized so that sub-micron cores can be produced to create fibers that have single-mode operation.