Early detection of neurodegeneration in brain ischemia by manganese-enhanced MRI

This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to detect neurodegenerative changes in two models of brain ischemia, photothrombotic cortical injury (PCI) and transient middle cerebral artery occlusion (MCAO) in rodents. After systemic Mn 2+ injection to both ischemic models, a close pattern of Tl-weighted hyperintensity was observed throughout different brain regions in comparison to the distribution of GFAP, MnSOD and GS immunoreactivities, whereby conventional MRI could hardly detect such. In addition, the infarct volumes in the posterior parts of the brain had significantly reduced after Mn 2+ injection to the MCAO model. It is suggested that exogenous Mn 2+ injection may provide enhanced MEMRI detection of oxidative stress and gliosis early after brain ischemia. Manganese may also mediate infarctions at remote brain regions in transient focal cerebral ischemia before delayed secondary damage takes place. © 2008 IEEE.published_or_final_versionThe 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS) 2008, Vancouver, BC., 20-25 August 2008. in Proceedings of the 30th EMBS, 2008, p. 3884-388

Mesenchymal stromal cells rescue disc degeneration and function via suppression of fibrotic events

DMM 2011 entitled: Re-engineering Regenerative MedicinePoster Session - Orthopedic Regeneration: no. 92Chronic back pain and neuropathological conditions such as spondylomyelopathy and radiculopathy are associated with degeneration of the intervertebral discs in spinal column. Human and animal studies imply a role of fibrosis in the degeneration process. Mesenchymal stromal cells (MSCs) possess anti-fibrotic activities. We investigated if MSCs elicit disc regeneration through modulating fibrotic events. Skeletally mature rabbits with injury-induced lumbar disc degeneration were randomized to receive intradiscal engraftment of bone marrow-derived MSCs or control vehicle. Disc degeneration status was evaluated by MRI and radiographs. We showed that MSCs regenerated the disc along with a recovery …postprin

Heterogeneity of fractional anisotropy and mean diffusivity measurements by in vivo diffusion tensor imaging in normal human hearts

Background: Cardiac diffusion tensor imaging (cDTI) by cardiovascular magnetic resonance has the potential to assess microstructural changes through measures of fractional anisotropy (FA) and mean diffusivity (MD). However, normal variation in regional and transmural FA and MD is not well described. Methods: Twenty normal subjects were scanned using an optimised cDTI sequence at 3T in systole. FA and MD were quantified in 3 transmural layers and 4 regional myocardial walls. Results: FA was higher in the mesocardium (0.46 ±0.04) than the endocardium (0.40 ±0.04, p≤0.001) and epicardium (0.39 ±0.04, p≤0.001). On regional analysis, the FA in the septum was greater than the lateral wall (0.44 ±0.03 vs 0.40 ±0.05 p = 0.04). There was a transmural gradient in MD increasing towards the endocardium (epicardium 0.87 ±0.07 vs endocardium 0.91 ±0.08×10-3 mm2/s, p = 0.04). With the lateral wall (0.87 ± 0.08×10-3 mm2/s) as the reference, the MD was higher in the anterior wall (0.92 ±0.08×10-3 mm2/s, p = 0.016) and septum (0.92 ±0.07×10-3 mm2/s, p = 0.028). Transmurally the signal to noise ratio (SNR) was greatest in the mesocardium (14.5 ±2.5 vs endocardium 13.1 ±2.2, p<0.001; vs epicardium 12.0 ± 2.4, p<0.001) and regionally in the septum (16.0 ±3.4 vs lateral wall 11.5 ± 1.5, p<0.001). Transmural analysis suggested a relative reduction in the rate of change in helical angle (HA) within the mesocardium. Conclusions: In vivo FA and MD measurements in normal human heart are heterogeneous, varying significantly transmurally and regionally. Contributors to this heterogeneity are many, complex and interactive, but include SNR, variations in cardiac microstructure, partial volume effects and strain. These data indicate that the potential clinical use of FA and MD would require measurement standardisation by myocardial region and layer, unless pathological changes substantially exceed the normal variation identified

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

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Measurement of top quark–antiquark pair production in association with a W or Z boson in pp collisions at √s=8 TeV

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Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

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Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

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Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

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Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe