Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions

<p>Abstract</p> <p>Background</p> <p>High-throughput methods for detecting protein-protein interactions enable us to obtain large interaction networks, and also allow us to computationally identify the associations of proteins as protein complexes. Although there are methods to extract protein complexes as sets of proteins from interaction networks, the extracted complexes may include false positives because they do not account for the structural limitations of the proteins and thus do not check that the proteins in the extracted complex can simultaneously bind to each other. In addition, there have been few searches for deeper insights into the protein complexes, such as of the topology of the protein-protein interactions or into the domain-domain interactions that mediate the protein interactions.</p> <p>Results</p> <p>Here, we introduce a combinatorial approach for prediction of protein complexes focusing not only on determining member proteins in complexes but also on the DDI/PPI organization of the complexes. Our method analyzes complex candidates predicted by the existing methods. It searches for optimal combinations of domain-domain interactions in the candidates based on an assumption that the proteins in a candidate can form a true protein complex if each of the domains is used by a single protein interaction. This optimization problem was mathematically formulated and solved using binary integer linear programming. By using publicly available sets of yeast protein-protein interactions and domain-domain interactions, we succeeded in extracting protein complex candidates with an accuracy that is twice the average accuracy of the existing methods, MCL, MCODE, or clustering coefficient. Although the configuring parameters for each algorithm resulted in slightly improved precisions, our method always showed better precision for most values of the parameters.</p> <p>Conclusions</p> <p>Our combinatorial approach can provide better accuracy for prediction of protein complexes and also enables to identify both direct PPIs and DDIs that mediate them in complexes.</p

Epidemiology of plasmid-mediated quinolone resistance in salmonella enterica serovar typhimurium isolates from food-producing animals in Japan

A total of 225 isolates of Salmonella enterica serovar Typhimurium from food-producing animals collected between 2003 and 2007 were examined for the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants, namely qnrA, qnrB, qnrC, qnrD, qnrS, qepA and aac(6')Ib-cr, in Japan. Two isolates (0.8%) of S. Typhimurium DT104 from different dairy cows on a single farm in 2006 and 2007 were found to have qnrS1 on a plasmid of approximately 9.6-kbp. None of the S. Typhimurium isolates had qnrA, qnrB, qnrC, qnrD, qepA and acc(6')-Ib-cr. Currently in Japan, the prevalence of the PMQR genes among S. Typhimurium isolates from food animals may remain low or restricted. The PFGE profile of two S. Typhimurium DT104 isolates without qnrS1 on the farm in 2005 had an identical PFGE profile to those of two S. Typhimurium DT104 isolates with qnrS1. The PFGE analysis suggested that the already existing S. Typhimurium DT104 on the farm fortuitously acquired the qnrS1 plasmid

Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis

As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis

MAXI GSC observations of a spectral state transition in the black hole candidate XTE J1752-223

We present the first results on the black hole candidate XTE J1752-223 from the Gas Slit Camera (GSC) on-board the Monitor of All-sky X-ray Image (MAXI) on the International Space Station. Including the onset of the outburst reported by the Proportional Counter Array on-board the Rossi X-ray Timing Explorer on 2009 October 23, the MAXI/GSC has been monitoring this source approximately 10 times per day with a high sensitivity in the 2-20 keV band. XTE J1752-223 was initially in the low/hard state during the first 3 months. An anti-correlated behavior between the 2-4 keV and 4-20 keV bands were observed around January 20, 2010, indicating that the source exhibited the spectral transition to the high/soft state. A transient radio jet may have been ejected when the source was in the intermediate state where the spectrum was roughly explained by a power-law with a photon index of 2.5-3.0. The unusually long period in the initial low/hard state implies a slow variation in the mass accretion rate, and the dramatic soft X-ray increase may be explained by a sudden appearance of the accretion disk component with a relatively low innermost temperature (0.4-0.7 keV). Such a low temperature might suggest that the maximum accretion rate was just above the critical gas evaporation rate required for the state transition.Comment: Publication of Astronomical Society of Japan Vol.62, No.5 (2010) [in print

Bright X-ray flares from the BL Lac object Mrk 421, detected with MAXI in 2010 January and February

Strong X-ray flares from the blazar Mrk 421 were detected in 2010 January and February through the 7 month monitoring with the MAXI GSC. The maximum 2 -- 10 keV flux in the January and February flares was measured as 120 +- 10 mCrab and 164 +- 17 mCrab respectively; the latter is the highest among those reported from the object. A comparison of the MAXI and Swift BAT data suggests a convex X-ray spectrum with an approximated photon index of about 2. This spectrum is consistent with a picture that MAXI is observing near the synchrotron peak frequency. The source exhibited a spectral variation during these flares, slightly different from those in the previous observations, in which the positive correlation between the flux and hardness was widely reported. By equating the halving decay timescale in the January flare, $t_{\rm d} \sim 2.5 \times 10^{4}$ s, to the synchrotron cooling time, the magnetic field was evaluated as B = 0.045 G $(\delta/10)^{-1/3}$, where $\delta$ is the jet beaming factor. Assuming that the light crossing time of the emission region is shorter than the doubling rise time, $t_{\rm r} \lesssim 2 \times 10^{4}$ s, the region size was roughly estimated as $R < 6 \times 10^{15}$ cm $(\delta/10)$. These are consistent with the values previously reported. For the February flare, the rise time, $t_{\rm r} < 1.3 \times 10^{5}$ s, gives a loose upper limit on the size as $R < 4 \times 10^{16}$ cm $(\delta/10)$, although the longer decay time $t_{\rm d} \sim 1.4 \times 10^{5}$ s, indicates B = 0.015 G $(\delta/10)^{-1/3}$, which is weaker than the previous results. This could be reconciled by invoking a scenario that this flare is a superposition of unresolved events with a shorter timescale.Comment: 14 pages, 4 figures, accepted for PASJ (Vol. 62 No. 6

A Large X-ray Flare from a Single Weak-lined T Tauri Star TWA-7 Detected with MAXI GSC

We present a large X-ray flare from a nearby weak-lined T Tauri star TWA-7 detected with the Gas Slit Camera (GSC) on the Monitor of All-sky X-ray Image (MAXI). The GSC captured X-ray flaring from TWA-7 with a flux of $3\times10^{-9}$ ergs cm$^{-2}$ s$^{-1}$ in 2--20 keV band during the scan transit starting at UT 2010-09-07 18:24:30.The estimated X-ray luminosity at the scan in the energy band is 3$\times10^{32}$ ergs s$^{-1}$,indicating that the event is among the largest X-ray flares fromT Tauri stars.Since MAXI GSC monitors a target only during a scan transit of about a minute per 92 min orbital cycle, the luminosity at the flare peak might have been higher than that detected. At the scan transit, we observed a high X-ray-to-bolometric luminosity ratio, log $L_{\rm X}/L_{\rm bol}$ = $-0.1^{+0.2}_{-0.3}$; i.e., the X-ray luminosity is comparable to the bolometric luminosity. Since TWA-7 has neither an accreting disk nor a binary companion, the observed event implies that none of those are essential to generate such big flares in T Tauri stars.Comment: 4 pages, 2 figures, 1 table accepted for publication in PAS

A Shock-Induced Pair of Superbubbles in the High-Redshift Powerful Radio Galaxy MRC 0406-244

We present new optical spectroscopy of the high-redshift powerful radio galaxy MRC 0406$-$244 at redshift of 2.429. We find that the two extensions toward NW and SE probed in the rest-frame ultraviolet image are heated mainly by the nonthermal continuum of the active galactic nucleus. However, each extension shows a shell-like morphology, suggesting that they are a pair of superbubbles induced by the superwind activity rather than by the interaction between the radio jet and the ambient gas clouds. If this is the case, the intense starburst responsible for the formation of superbubbles could occur $\sim 1 \times 10^9$ yr ago. On the other hand, the age of the radio jets may be of the order of $\sim 10^6$ yr, being much shorter than the starburst age. Therefore, the two events, i.e., the starburst and the radio-jet activities, are independent phenomena. However, their directions of the expanding motions could be governed by the rotational motion of the gaseous component in the host galaxy. This idea appears to explain the alignment effect of MRC 0406$-$244.Comment: 4 pages (emulateapj.sty), Fig. 1 (jpeg) + Fig.2 (eps). Accepted for publications in ApJ (Letters

Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity

金沢大学医薬保健研究域医学系A series of events initiated by glutamate-receptor interaction perturbs cellular homeostasis resulting in elevation of intracellular free calcium and cell death. Cells subject to such environmental change express stress proteins, which contribute importantly to maintenance of metabolic homeostasis and viability. We show that an inducible chaperone present in endoplasmic reticulum (ER), the 150-kDa oxygen-regulated protein (ORP150), is expressed both in the human brain after seizure attack and in mouse hippocampus after kainate administration. Using mice heterozygous for ORP150 deficiency, exposure to excitatory stimuli caused hippocampal neurons to display exaggerated elevation of cytosolic calcium accompanied by activation of μ-calpain and cathepsin B, as well as increased vulnerability to glutamate-induced cell death in vitro and decreased survival to kainate in vivo. In contrast, targeted neuronal overexpression of ORP150 suppressed each of these events and enhanced neuronal and animal survival in parallel with diminished seizure intensity. Studies using cultured hippocampal neurons showed that ORP150 regulates cytosolic free calcium and activation of proteolytic pathways causing cell death in neurons subject to excitatory stress. Our data underscore a possible role for ER stress in glutamate toxicity and pinpoint a key ER chaperone, ORP150, which contributes to the stress response critical for neuronal survival