Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data

Background: Disordered proteins need to be expressed to carry out specified functions; however, their accumulation in the cell can potentially cause major problems through protein misfolding and aggregation. Gene expression levels, mRNA decay rates, microRNA (miRNA) targeting and ubiquitination have critical roles in the degradation and disposal of human proteins and transcripts. Here, we describe a study examining these features to gain insights into the regulation of disordered proteins. Results: In comparison with ordered proteins, disordered proteins have a greater proportion of predicted ubiquitination sites. The transcripts encoding disordered proteins also have higher proportions of predicted miRNA target sites and higher mRNA decay rates, both of which are indicative of the observed lower gene expression levels. The results suggest that the disordered proteins and their transcripts are present in the cell at low levels and/or for a short time before being targeted for disposal. Surprisingly, we find that for a significant proportion of highly disordered proteins, all four of these trends are reversed. Predicted estimates for miRNA targets, ubiquitination and mRNA decay rate are low in the highly disordered proteins that are constitutively and/or highly expressed. Conclusions: Mechanisms are in place to protect the cell from these potentially dangerous proteins. The evidence suggests that the enrichment of signals for miRNA targeting and ubiquitination may help prevent the accumulation of disordered proteins in the cell. Our data also provide evidence for a mechanism by which a significant proportion of highly disordered proteins (with high expression levels) can escape rapid degradation to allow them to successfully carry out their function

Laboratory capture, isolation and analysis of microparticles in aerogel: Preparation for the return of Stardust

We present observations from the laboratory capture of particles in aerogel. The paper focuses on a possible extraction technique and the bulk mineral characterization of the captured material using non-destructive analytical techniques

Giant gravitons in AdS/CFT (I): matrix model and back reaction

In this article we study giant gravitons in the framework of AdS/CFT correspondence. First, we show how to describe these configurations in the CFT side using a matrix model. In this picture, giant gravitons are realized as single excitations high above a Fermi sea, or as deep holes into it. Then, we give a prescription to define quasi-classical states and we recover the known classical solution associated to the CFT dual of a giant graviton that grows in AdS. Second, we use the AdS/CFT dictionary to obtain the supergravity boundary stress tensor of a general state and to holographically reconstruct the bulk metric, obtaining the back reaction of space-time. We find that the space-time response to all the supersymmetric giant graviton states is of the same form, producing the singular BPS limit of the three charge Reissner-Nordstr\"om-AdS black holes. While computing the boundary stress tensor, we comment on the finite counterterm recently introduced by Liu and Sabra, and connect it to a scheme-dependent conformal anomaly.Comment: 28 pages, JHEP3 class. v2: typos corrected and references adde

ISPIDER Central: an integrated database web-server for proteomics

Despite the growing volumes of proteomic data, integration of the underlying results remains problematic owing to differences in formats, data captured, protein accessions and services available from the individual repositories. To address this, we present the ISPIDER Central Proteomic Database search (http://www.ispider.manchester.ac.uk/cgi-bin/ProteomicSearch.pl), an integration service offering novel search capabilities over leading, mature, proteomic repositories including PRoteomics IDEntifications database (PRIDE), PepSeeker, PeptideAtlas and the Global Proteome Machine. It enables users to search for proteins and peptides that have been characterised in mass spectrometry-based proteomics experiments from different groups, stored in different databases, and view the collated results with specialist viewers/clients. In order to overcome limitations imposed by the great variability in protein accessions used by individual laboratories, the European Bioinformatics Institute's Protein Identifier Cross-Reference (PICR) service is used to resolve accessions from different sequence repositories. Custom-built clients allow users to view peptide/protein identifications in different contexts from multiple experiments and repositories, as well as integration with the Dasty2 client supporting any annotations available from Distributed Annotation System servers. Further information on the protein hits may also be added via external web services able to take a protein as input. This web server offers the first truly integrated access to proteomics repositories and provides a unique service to biologists interested in mass spectrometry-based proteomics

BPS Electromagnetic Waves on Giant Gravitons

We find new 1/8-BPS giant graviton solutions in $AdS_5 \times S^5$, carrying three angular momenta along $S^5$, and investigate their properties. Especially, we show that nonzero worldvolume gauge fields are admitted preserving supersymmetry. These gauge field modes can be viewed as electromagnetic waves along the compact D3 brane, whose Poynting vector contributes to the BPS angular momenta. We also analyze the (nearly-)spherical giant gravitons with worldvolume gauge fields in detail. Expressing the $S^3$ in Hopf fibration ($S^1$ fibred over $S^2$), the wave propagates along the $S^1$ fiber.Comment: 25 pages, no figures, v2: references adde

A randomized trial of glutamine and antioxidants in critically ill patients.

BACKGROUND: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting. METHODS: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance. RESULTS: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83). CONCLUSIONS: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.)

The three-dimensional structure of Saturn's E ring

Saturn's diffuse E ring consists of many tiny (micron and sub-micron) grains of water ice distributed between the orbits of Mimas and Titan. Various gravitational and non-gravitational forces perturb these particles' orbits, causing the ring's local particle density to vary noticeably with distance from the planet, height above the ring-plane, hour angle and time. Using remote-sensing data obtained by the Cassini spacecraft in 2005 and 2006, we investigate the E-ring's three-dimensional structure during a time when the Sun illuminated the rings from the south at high elevation angles (> 15 degrees). These observations show that the ring's vertical thickness grows with distance from Enceladus' orbit and its peak brightness density shifts from south to north of Saturn's equator plane with increasing distance from the planet. These data also reveal a localized depletion in particle density near Saturn's equatorial plane around Enceladus' semi-major axis. Finally, variations are detected in the radial brightness profile and the vertical thickness of the ring as a function of longitude relative to the Sun. Possible physical mechanisms and processes that may be responsible for some of these structures include solar radiation pressure, variations in the ambient plasma, and electromagnetic perturbations associated with Saturn's shadow.Comment: 42 Pages, 13 Figures, modified to include minor proof correction

The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis.

A previous study showed that, in carriers of the apolipoprotein E (APOE) genotype ε3/ε3 or ε3/ε4, the presence of a very long (VL) polyT repeat allele in "translocase of outer mitochondrial membrane 40" (TOMM40) was less frequent in patients with sporadic inclusion body myositis (sIBM) compared with controls and associated with a later age of sIBM symptom onset, suggesting a protective effect of this haplotype. To further investigate the influence of these genetic factors in sIBM, we analyzed a large sIBM cohort of 158 cases as part of an International sIBM Genetics Study. No significant association was found between APOE or TOMM40 genotypes and the risk of developing sIBM. We found that the presence of at least 1 VL polyT repeat allele in TOMM40 was significantly associated with about 4 years later onset of sIBM symptoms. The age of onset was delayed by 5 years when the patients were also carriers of the APOE genotype ε3/ε3. In addition, males were likely to have a later age of onset than females. Therefore, the TOMM40 VL polyT repeat, although not influencing disease susceptibility, has a disease-modifying effect on sIBM, which can be enhanced by the APOE genotype ε3/ε3