The protein information and property explorer: an easy-to-use, rich-client web application for the management and functional analysis of proteomic data

Motivation: Mass spectrometry experiments in the field of proteomics produce lists containing tens to thousands of identified proteins. With the protein information and property explorer (PIPE), the biologist can acquire functional annotations for these proteins and explore the enrichment of the list, or fraction thereof, with respect to functional classes. These protein lists may be saved for access at a later time or different location. The PIPE is interoperable with the Firegoose and the Gaggle, permitting wide-ranging data exploration and analysis. The PIPE is a rich-client web application which uses AJAX capabilities provided by the Google Web Toolkit, and server-side data storage using Hibernate. Availability: http://pipe.systemsbiology.net Contact: [email protected]

Role of interband scattering in neutron irradiated MgB2_2 thin films by Scanning Tunneling Spectroscopy measurements

A series of MgB$_2$ thin films systematically disordered by neutron irradiation have been studied by Scanning Tunneling Spectroscopy. The c-axis orientation of the films allowed a reliable determination of local density of state of the $\pi$ band. With increasing disorder, the conductance peak moves towards higher voltages and becomes lower and broader, indicating a monotonic increase of the $\pi$ gap and of the broadening parameter. These results are discussed in the frame of two-band superconductivity.Comment: The text will be submitted in Latex format, and the corresponding pdf file should take 6 pages. There are 5 figures (eps files submitted) and 1 tabl

Defining potentially conserved RNA regulons of homologous zinc-finger RNA-binding proteins

Glucose inhibition of gluconeogenic growth suppressor 2 protein (Gis2p) and zinc-finger protein 9 (ZNF9) are conserved yeast and human zinc-finger proteins. The function of yeast Gis2p is unknown, but human ZNF9 has been reported to bind nucleic acids, and mutations in the ZNF9 gene cause the neuromuscular disease myotonic dystrophy type 2. To explore the impact of these proteins on RNA regulation, we undertook a systematic analysis of the RNA targets and of the global implications for gene expression

Disentangling genetic and environmental effects on the proteotypes of individuals

Proteotypes, like genotypes, have been found to vary between individuals in several studies, but consistent molecular functional traits across studies remain to be quantified. In a meta-analysis of 11 proteomics datasets from humans and mice, we use co-variation of proteins in known functional modules across datasets and individuals to obtain a consensus landscape of proteotype variation. We find that individuals differ considerably in both protein complex abundances and stoichiometry. We disentangle genetic and environmental factors impacting these metrics, with genetic sex and specific diets together explaining 13.5% and 11.6% of the observed variation of complex abundance and stoichiometry, respectively. Sex-specific differences, for example, include various proteins and complexes, where the respective genes are not located on sex-specific chromosomes. Diet-specific differences, added to the individual genetic backgrounds, might become a starting point for personalized proteotype modulation toward desired features

Bupivacaine crystal deposits after long-term epidural infusion

The case of a 45-year-old male patient (body weight 52kg, height 1.61m) with a locally invasive gastric carcinoma infiltrating into the retroperitoneal space is reported. Because of severe cancer pain a tunnelled thoracic epidural catheter (EC) was placed at thoracic spinal level 7/8 and a local anesthetic (LA) mixture of bupivacaine 0.25 % and morphine 0.005 % was infused continuously at 6mlh−1. To optimize pain therapy the concentration was doubled (bupivacaine 0.5 %, morphine 0.01 %) 3 months later but the infusion rate was reduced to 3mlh−1 thus the total daily dose did not change. The patient died 6 months after initiation of the epidural analgesia from the underlying disease. The total amount of bupivacaine infused was 69g and of morphine 1.37g. The patient never reported any neurological complications. The autopsy revealed large white crystalline deposits in the thoracic epidural space which were identified as bupivacaine base by infrared spectrometry. Morphine could not be detected. A histological examination showed unreactive fatty tissue necrosis within the crystalline deposits but nerve tissue could not be identified. It is concluded that the bupivacaine crystalline deposits arose due to precipitation but the clinical significance with regard to sensory level and neuraxial tissue toxicity is unknow

Neutron Irradiation of Mg11B2 : From the Enhancement to the Suppression of Superconducting Properties

In this letter we present the effect of neutron irradiation up to fluences of 3.9 1019 n/cm2 on the superconducting properties of MgB2. In order to obtain a disorder structure homogeneously distributed, the experiment was carried out on bulk samples prepared with the 11B isotope. Up to fluences of 1018 n/cm2 the critical temperature is slightly diminished (36 K) and the superconducting properties are significantly improved; the upper critical field is increased from 13.5 T to 20.3 T at 12 K and the irreversibility field is doubled at 5 K. For larger neutron fluences the critical temperature is suppressed down to 12 K and the superconducting properties come out strongly degraded.Comment: 13 pages, 4 figures. Submitted to Appl.Phys.Let

Chemical cross-linking/mass spectrometry targeting acidic residues in proteins and protein complexes

The study of proteins and protein complexes using chemical cross-linking followed by the MS identification of the cross-linked peptides has found increasingly widespread use in recent years. Thus far, such analyses have used almost exclusively homobifunctional, amine-reactive cross-linking reagents. Here we report the development and application of an orthogonal cross-linking chemistry specific for carboxyl groups. Chemical cross-linking of acidic residues is achieved using homobifunctional dihydrazides as cross-linking reagents and a coupling chemistry at neutral pH that is compatible with the structural integrity of most protein complexes. In addition to cross-links formed through insertion of the dihydrazides with different spacer lengths, zero-length cross-link products are also obtained, thereby providing additional structural information. We demonstrate the application of the reaction and the MS identification of the resulting cross-linked peptides for the chaperonin TRiC/CCT and the 26S proteasome. The results indicate that the targeting of acidic residues for cross-linking provides distance restraints that are complementary and orthogonal to those obtained from lysine cross-linking, thereby expanding the yield of structural information that can be obtained from cross-linking studies and used in hybrid modeling approaches

Enhanced flux pinning in neutron irradiated MgB2

We study the effect of neutron irradiation on the critical current density Jc of isotopically pure polycrystalline Mg11B2 samples. For fluences in the range 1017-1018 cm-2, Jc is enhanced and its dependence on magnetic field is significantly improved: we demonstrate that, in this regime, point-like pinning centers are effectively introduced in the system proportionally to the neutron fluence. Instead, for larger fluences, a strong suppression of the critical temperature accompanied by a decrease of both the upper critical field Bc2 and Jc is found.Comment: 13 pages, 3 igure

Global alignment of protein-protein interaction networks by graph matching methods

Aligning protein-protein interaction (PPI) networks of different species has drawn a considerable interest recently. This problem is important to investigate evolutionary conserved pathways or protein complexes across species, and to help in the identification of functional orthologs through the detection of conserved interactions. It is however a difficult combinatorial problem, for which only heuristic methods have been proposed so far. We reformulate the PPI alignment as a graph matching problem, and investigate how state-of-the-art graph matching algorithms can be used for that purpose. We differentiate between two alignment problems, depending on whether strict constraints on protein matches are given, based on sequence similarity, or whether the goal is instead to find an optimal compromise between sequence similarity and interaction conservation in the alignment. We propose new methods for both cases, and assess their performance on the alignment of the yeast and fly PPI networks. The new methods consistently outperform state-of-the-art algorithms, retrieving in particular 78% more conserved interactions than IsoRank for a given level of sequence similarity. Availability:http://cbio.ensmp.fr/proj/graphm\_ppi/, additional data and codes are available upon request. Contact: [email protected]: Preprint versio