Calibrating E-values for MS2 database search methods

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Detection of co-eluted peptides using database search methods

<p>Abstract</p> <p>Background</p> <p>Current experimental techniques, especially those applying liquid chromatography mass spectrometry, have made high-throughput proteomic studies possible. The increase in throughput however also raises concerns on the accuracy of identification or quantification. Most experimental procedures select in a given MS scan only a few relatively most intense parent ions, each to be fragmented (MS²) separately, and most other minor co-eluted peptides that have similar chromatographic retention times are ignored and their information lost.</p> <p>Results</p> <p>We have computationally investigated the possibility of enhancing the information retrieval during a given LC/MS experiment by selecting the two or three most intense parent ions for simultaneous fragmentation. A set of spectra is created via superimposing a number of MS²spectra, each can be identified by all search methods tested with high confidence, to mimick the spectra of co-eluted peptides. The generated convoluted spectra were used to evaluate the capability of several database search methods – SEQUEST, Mascot, X!Tandem, OMSSA, and RAId_DbS – in identifying true peptides from superimposed spectra of co-eluted peptides. We show that using these simulated spectra, all the database search methods will gain eventually in the number of true peptides identified by using the compound spectra of co-eluted peptides.</p> <p>Open peer review</p> <p>Reviewed by Vlad Petyuk (nominated by Arcady Mushegian), King Jordan and Shamil Sunyaev. For the full reviews, please go to the Reviewers' comments section.</p

Cosmology, Oscillating Physics and Oscilllating Biology

According to recent reports there is an excess correlation and an apparent regularity in the galaxy one-dimensional polar distribution with a characteristic scale of 128 $h^{-1}$ Mpc. This aparent spatial periodicity can be naturally explained by a time oscillation of the gravitational constant $G$. On the other hand, periodic growth features of bivalve and coral fossiles appear to show a periodic component in the time dependence of the number of days per year. In this letter we show that a time oscillating gravitational constant with similar period and amplitude can explain such a feature.Comment: 9 pages. latex using revtex. This revised version is supposed to be free of e-mail nois

A light-fronts approach to electron-positron pair production in ultrarelativistic heavy-ion collisions

We perform a gauge-transformation on the time-dependent Dirac equation describing the evolution of an electron in a heavy-ion collision to remove the explicit dependence on the long-range part of the interaction. We solve, in an ultra-relativistic limit, the gauged-transformed Dirac equation using light-front variables and a light-fronts representation, obtaining non-perturbative results for the free pair-creation amplitudes in the collider frame. Our result reproduces the result of second-order perturbation theory in the small charge limit while non-perturbative effects arise for realistic charges of the ions.Comment: 39 pages, Revtex, 7 figures, submitted to PR

Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein

The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

Multiband model of high Tc superconductors

We propose an extension to other high T_{c } compounds of a model introduced earlier for YBCO. In the ''self-doped'' compounds we assume that the doping part (namely the BiO, HgO, TlO planes in BSCCO, HBCCO, TBCCO respectively) is metallic, which leads to a multiband model. This assumption is supported by band structure calculations. Taking a repulsive pairing interaction between these doping bands and the CuO_{2} bands leads to opposite signs for the order parameter on these bands and to nodes whenever the Fermi surfaces of these bands cross. We show that in BSCCO the low temperature dependence of the penetration depth is reasonably accounted for. In this case the nodes are not located near the 45^{o} direction, which makes the experimental determination of the node locations an important test for our model. The situation in HBCCO and TBCCO is rather analogous to BSCCO. We consider the indications given by NMR and find that they rather favor a metallic character for the doping bands. Finally we discuss the cases of NCCO and LSCO which are not ''self-doped'' and where our model does not give nodes.Comment: 11 pages, revtex, 1 figure

Synovial changes detected by ultrasound in people with knee osteoarthritis - a meta-analysis of observational studies

Objectives To examine the prevalence of synovial effusion, synovial hypertrophy and positive Doppler signal (DS) detected by ultrasound (US) in people with knee osteoarthritis (OA) and/or knee pain compared to that in the general population. Method A systematic literature search was undertaken in Medline, EMBASE, Allied and Complementary Medicine, PubMed Web of Science, and SCOPUS databases in May 2015. Frequencies of US abnormalities in people with knee OA/pain, in the general population or asymptomatic controls were pooled using the random effects model. Publication bias and heterogeneity between studies were examined. Results Twenty four studies in people with knee pain/OA and five studies of the general population or asymptomatic controls met the inclusion criteria. The pooled prevalence of US effusion, synovial hypertrophy and positive DS in people with knee OA/pain were 51.5% (95% CI 40.2 to 62.8), 41.5% (26.3–57.5) and 32.7% (8.34–63.24), respectively, which were higher than those in the general population or asymptomatic controls (19.9% (95%CI 7.8–35.3%), 14.5% (0–58.81), and 15.8 (3.08–35.36), respectively). People with knee OA (ACR criteria or radiographic OA) had greater prevalence of US abnormalities than people with knee pain (P = 0.037, P = 0.010 and P = 0.009, respectively). Conclusions US detected effusion, synovial hypertrophy and DS are more common in people with knee OA/pain, compared to the general population. These abnormalities relate more to presence of OA structural changes than to pain

Pion interferometry in Au+Au collisions at sNN\sqrt{\mathrm{s}_{_{\mathrm{NN}}}} = 200 GeV

We present a systematic analysis of two-pion interferometry in Au+Au collisions at $\sqrt{s_{NN}}$ = 200 GeV using the STAR detector at RHIC. We extract the HBT radii and study their multiplicity, transverse momentum, and azimuthal angle dependence. The Gaussianess of the correlation function is studied. Estimates of the geometrical and dynamical structure of the freeze-out source are extracted by fits with blast wave parameterizations. The expansion of the source and its relation with the initial energy density distribution is studied.Comment: 21 pages, 30 figures. As published in Physics Review

Transverse-momentum dependent modification of dynamic texture in central Au+Au collisions at sqrt(S_NN)=200 GeV

Correlations in the hadron distributions produced in relativistic Au+Au collisions are studied in the discrete wavelet expansion method. The analysis is performed in the space of pseudorapidity (|eta| < 1) and azimuth (full 2 pi) in bins of transverse momentum (p_t) from 0.14 < p_t < 2.1 GeV/c. In peripheral Au+Au collisions a correlation structure ascribed to mini-jet fragmentation is observed. It evolves with collision centrality and p_t in a way not seen before which suggests strong dissipation of minijet fragmentation in the longitudinally-expanding medium.Comment: 6 pages, 3 figure, accepted as Phys.Rev.C Rapid Communication. This version fixes journal style issue