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

Hydrogen Bond Energies in Carboxylic Acids

A question of interest to the study of the chemisorption of carbon monoxide on iron is whether the carbon is desorbed with the same oxygen to which it was bonded prior to the adsorption. A mixture of C13O and CO18 in the desorbed gas in amounts greater than expected from normal abundance ratios shows that an intermolecular oxygen exchange occurs

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

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

Prednost parenteralne primjene Mi-ADMS pred DMSA u snižavanju tjelesnog opterećenja živom (203Hg) u štakora

The efficiency of meso-2,3-dirnercaptosuccinic acid (DMSA) and the mono-isoamyl ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) in decreasing 203Hg retention was evaluated in rats in relation to age and time of treatment. The experiments were performed on six-week- and seven- day-old Wistar rats, which received 203Hg by intraperitoneal administration. The chelators DMSA or Mi-ADMS were also administered intraperitoneally, twice, on two consecutive days, in doses of 0.25 mmol/kg body weight as early (0.5 and 24 h) or delayed treatment (24 and 48 h, or 48 and 72 h) after 203Hg administration. The retention of 203Hg was determined in the carcass, liver, kidneys and brain six days after administration using gamma scintillation counters (double crystal, well type). In all experimental conditions, regardless of the animals\u27 age and time of chelation therapy, Mi-ADMS was found to be superior to DMSA in reducing the body burden of 203Hg in whole body and organs. Mi-ADMS therefore seems to be a very promising chelator in the treatment of mercury poisoning.Procjenjivana je učinkovitost mezo-2,3-dimerkaptojantarne kiseline (DMSA) i monoizoamilnog estera mezo-2,3-dimerkaplojantarne kiseline (Mi-ADMS) u snižavanju opterećenja živom (203Hg) u štakora u odnosu na dob i vrijeme primjene. Pokusi su provedeni na šestotjednim ženkama i sedmodnevnim sisajućim bijelim štakorima Wistar iz uzgoja Instituta u Zagrebu, kojima je intraperi-tonejski davana 203Hg. Kelati DMSA i Mi-ADMS davani su, također intraperitonejski, dva dana zaredom u dozi od 0,25 mmol/kg tjelesne težine kao neposredna/rana primjena (El - 0,5 i 24 h) ili kao odgođena/kasna primjena (E2 - 24 i 48 h, E3 - 48 i 72 h) nakon davanja 203Hg. Retencija 203Hg mjerena je u karkasu (tijelo nakon odstranjenja probavila), u jetri, u bubrezima i u mozgu sest dana nakon primjene Hg u odgovarajućim gamascintilacijskim brojačima. U šestotjednih životinja i DMSA i Mi-ADMS primijenjeni kao rana terapija (El) snizili su retenciju 203Hg u karkasu i u organima u odnosu na vrijednosti u kontrolnih (netretiranih) životinja. Odgođena primjena (E2 i E3) jednog i drugog kelata snizila je retenciju 203Hg u karkasu i bubrezima, nije imala učinka na retenciju u jetri, a retenciju u mozgu snizio je samo Mi-ADMS. U sedmodnevne sisančadi oba kelata značajno su snizila tjelesnu retenciju 203Hg i nakon rane (El) i nakon kasne primjene (E2), a jedino DMSA u kasnijoj primjeni (E2) nije imao učinka na retenciju Hg u mozgu. U svim eksperimentalnim uvjetima neovisno o dobi životinja i vremenu kad je primijenjen kelat, terapija s Mi-ADMS bila je učinkovitija od DMSA u snižavanju tjelesnog opterećenja 203Hg u tijelu i u organima. To je glavni nalaz ovog istraživanja. Čini se da je Mi-ADMS kelat koji puno obećava u budućnosti kao lijek izbora u terapiji otrovanja živom

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

Tribo-corrosion mechanisms of stainless steel in soft drinks

Tribo-corrosion mechanisms of 316L Stainless Steel in slurries containing common household soft drinks have been studied through investigating the micro-abrasion-corrosion performance using a ball and disk apparatus which has been modified to measure the in-situ corrosion current during the abrasion process. The objective of this study was to evaluate the effect of pH and solution viscosity on the micro-abrasion-corrosion performance of the material. 316L Stainless Steel was selected because it is commonly used as a dental replacement material. This is an important area of work as the use of steel retainers as well as other stainless steel dental replacements is still widespread and the effectiveness of these devices will be determined by their tribological and tribo-corrosion performance. Additionally, an attempt has been made to investigate the importance of the pH and viscosity variables on the tribo-corrosive synergism, wastage and mechanism maps