Proteomic profiling of neuromas reveals alterations in protein composition and local protein synthesis in hyper-excitable nerves

Neuropathic pain may arise following peripheral nerve injury though the molecular mechanisms associated with this are unclear. We used proteomic profiling to examine changes in protein expression associated with the formation of hyper-excitable neuromas derived from rodent saphenous nerves. A two-dimensional difference gel electrophoresis ( 2D-DIGE) profiling strategy was employed to examine protein expression changes between developing neuromas and normal nerves in whole tissue lysates. We found around 200 proteins which displayed a > 1.75-fold change in expression between neuroma and normal nerve and identified 55 of these proteins using mass spectrometry. We also used immunoblotting to examine the expression of low-abundance ion channels Nav1.3, Nav1.8 and calcium channel alpha 2 delta-1 subunit in this model, since they have previously been implicated in neuronal hyperexcitability associated with neuropathic pain. Finally, S(35)methionine in vitro labelling of neuroma and control samples was used to demonstrate local protein synthesis of neuron-specific genes. A number of cytoskeletal proteins, enzymes and proteins associated with oxidative stress were up-regulated in neuromas, whilst overall levels of voltage-gated ion channel proteins were unaffected. We conclude that altered mRNA levels reported in the somata of damaged DRG neurons do not necessarily reflect levels of altered proteins in hyper-excitable damaged nerve endings. An altered repertoire of protein expression, local protein synthesis and topological re-arrangements of ion channels may all play important roles in neuroma hyper-excitability

Rethinking the sub-Antarctic terrestrial N-cycle : evidence for organic N acquisition by Marion Island grasses

Please read abstract in the article.The South African National Research Foundation (NRF), South African National Antarctic Programme (SANAP). Open access funding provided by University of Cape Town.http://link.springer.com/journal/300hj2024Plant Production and Soil ScienceSDG-15:Life on lan

Rebirth of X-ray Emission from the Born-Again Planetary Nebula A 30

The planetary nebula (PN) A30 is believed to have undergone a very late thermal pulse resulting in the ejection of knots of hydrogen-poor material. Using HST images we have detected the angular expansion of these knots and derived an age of 850+280-150 yr. To investigate the spectral and spatial properties of the soft X-ray emission detected by ROSAT, we have obtained Chandra and XMM-Newton observations of A30. The X-ray emission from A30 can be separated into two components: a point-source at the central star and diffuse emission associated with the hydrogen-poor knots and the cloverleaf structure inside the nebular shell. To help us assess the role of the current stellar wind in powering this X-ray emission, we have determined the stellar parameters of the central star of A 30 using a non-LTE model fit to its optical and UV spectrum. The spatial distribution and spectral properties of the diffuse X-ray emission is suggestive that it is generated by the post-born-again and present fast stellar winds interacting with the hydrogen-poor ejecta of the born-again event. This emission can be attributed to shock-heated plasma, as the hydrogen-poor knots are ablated by the stellar winds, under which circumstances the efficient mass-loading of the present fast stellar wind raises its density and damps its velocity to produce the observed diffuse soft X-rays. Charge transfer reactions between the ions of the stellar winds and material of the born-again ejecta has also been considered as a possible mechanism for the production of diffuse X-ray emission, and upper limits on the expected X-ray production by this mechanism have been derived. The origin of the X-ray emission from the central star of A 30 is puzzling: shocks in the present fast stellar wind and photospheric emission can be ruled out, while the development of a new, compact hot bubble confining the fast stellar wind seems implausible.Comment: 29 pages, 11 figures, 4 tables; accepted for publication by Ap

Multidimensional Conservation Laws: Overview, Problems, and Perspective

Some of recent important developments are overviewed, several longstanding open problems are discussed, and a perspective is presented for the mathematical theory of multidimensional conservation laws. Some basic features and phenomena of multidimensional hyperbolic conservation laws are revealed, and some samples of multidimensional systems/models and related important problems are presented and analyzed with emphasis on the prototypes that have been solved or may be expected to be solved rigorously at least for some cases. In particular, multidimensional steady supersonic problems and transonic problems, shock reflection-diffraction problems, and related effective nonlinear approaches are analyzed. A theory of divergence-measure vector fields and related analytical frameworks for the analysis of entropy solutions are discussed.Comment: 43 pages, 3 figure

Parton coalescence at RHIC

Using a covariant coalescence model, we study hadron production in relativistic heavy ion collisions from both soft partons in the quark-gluon plasma and hard partons in minijets. Including transverse flow of soft partons and independent fragmentation of minijet partons, the model is able to describe available experimental data on pion, kaon, and antiproton spectra. The resulting antiproton to pion ratio is seen to increase at low transverse momenta and reaches a value of about one at intermediate transverse momenta, as observed in experimental data at RHIC. A similar dependence of the antikaon to pion ratio on transverse momentum is obtained, but it reaches a smaller value at intermediate transverse momenta. At high transverse momenta, the model predicts that both the antiproton to pion and the antikaon to pion ratio decrease and approach those given by the perturbative QCD. Both collective flow effect and coalescence of minijet partons with partons in the quark-gluon plasma affect significantly the spectra of hadrons with intermediate transverse momenta. Elliptic flows of protons, Lambdas, and Omegas have also been evaluated from partons with elliptic flows extracted from fitting measured pion and kaon elliptic flows, and they are found to be consistent with available experimental data.Comment: 12 pages, 11 figure

Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

We report a high precision measurement of the transverse single spin asymmetry $A_N$ at the center of mass energy $\sqrt{s}=200$ GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The $A_N$ was measured in the four-momentum transfer squared $t$ range $0.003 \leqslant |t| \leqslant 0.035$ \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of $A_N$ and its $t$-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this $\sqrt{s}$, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk