The interaction of unfolding α-lactalbumin and malate dehydrogenase with the molecular chaperone αB-crystallin: a light and X-ray scattering investigation

Purpose: The molecular chaperone αB-crystallin is found in high concentrations in the lens and is present in all major body tissues. Its structure and the mechanism by which it protects its target protein from aggregating and precipitating are not known. Methods: Dynamic light scattering and X-ray solution scattering techniques were used to investigate structural features of the αB-crystallin oligomer when complexed with target proteins under mild stress conditions, i.e., reduction of α- lactalbumin at 37 °C and malate dehydrogenase when heated at 42 °C. In this investigation, the size, shape and particle distribution of the complexes were determined in real-time following the induction of stress. Results: Overall, it is observed that the mass distribution, hydrodynamic radius, and spherical shape of the αB-crystallin oligomer do not alter significantly when it complexes with its target protein. Conclusions: The data are consistent with the target protein being located in the outer protein shell of the αB-crystallin oligomer where it is readily accessible for possible refolding via the action of other molecular chaperones. © 2010 Molecular Vision

The HUPO-PSI standardized spectral library format

More and more proteomics datasets are becoming available in public repositories. The knowledge embedded in these datasets can be used to improve peptide identification workflows. Spectral library searching provides a straightforward method to boost identification rates using previously identified spectra. Alternatively, machine learning methods can learn from these spectra to accurately predict the behavior of peptides in a liquid chromatography-mass spectrometry system. At the basis of both approaches are spectral libraries: Unified collections of previously identified spectra. Organizations and projects such as the National Institute of Standards and Technology (NIST), the Global Proteome Machine, PeptideAtlas, PRIDE Archive and MassIVE have all compiled spectral libraries for a multitude of species and experimental setups. A large obstacle, however, is that each organization provides libraries in a different file format. At the software level the problem propagates (if not expands), as different software tools require different file formats. The solution is a standardized spectral library format that is sufficiently flexible to meet all users' demands, but that is also standardized enough to be usable across environments and software packages. This balance is achieved by setting up a standardized framework and a controlled vocabulary with metadata terms, and allow the format to be represented in different forms, such as plain text, JSON and HDF. So far, the required (and optional) meta data has been compiled and added to the PSI-MS ontology, and versions of the text and JSON representations have been drafted. The tabular and HDF representations of the format are in development, as well as converters and validators in various programming languages

GeneDB--an annotation database for pathogens.

GeneDB (http://www.genedb.org) is a genome database for prokaryotic and eukaryotic pathogens and closely related organisms. The resource provides a portal to genome sequence and annotation data, which is primarily generated by the Pathogen Genomics group at the Wellcome Trust Sanger Institute. It combines data from completed and ongoing genome projects with curated annotation, which is readily accessible from a web based resource. The development of the database in recent years has focused on providing database-driven annotation tools and pipelines, as well as catering for increasingly frequent assembly updates. The website has been significantly redesigned to take advantage of current web technologies, and improve usability. The current release stores 41 data sets, of which 17 are manually curated and maintained by biologists, who review and incorporate data from the scientific literature, as well as other sources. GeneDB is primarily a production and annotation database for the genomes of predominantly pathogenic organisms

The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants

The complete Stenotrophomonas maltophilia genome sequence suggests that it can act as a reservoir of antibiotic resistance determinants

TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling

<p>Abstract</p> <p>Background</p> <p><it>TMPRSS2-ERG </it>gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although <it>TMPRSS2-ERG </it>fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear.</p> <p>Methods</p> <p>We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays.</p> <p>Results</p> <p>Comparison of gene expression levels among <it>TMPRSS2-ERG </it>fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like <it>CRISP3 </it>were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in <it>TMPRSS2-ERG </it>fusion-positive tumors.</p> <p>Conclusions</p> <p>The <it>TMPRSS2-ERG </it>gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy.</p

The wrong side of the tracks: Starting school in a socially disadvantaged London borough

Substantial evidence exists that social circumstances can affect children’s language development. As a result many children in socially deprived areas start school with delayed language, which may persist and adversely affect their attainment. We assessed the language of children in seven reception classes in a London (UK) borough and followed the progress of children with English as their first language (E1L) and with English as an additional language (EAL) during their first 2 years at school. Significant differences were found between schools. The effect of social factors on performance was reflected in a high correlation between the mean language score for each school and the percentage of children in the school receiving the pupil premium. Many of the children with EAL had very low scores reflecting their limited exposure to English prior to starting school. Most of these children attended schools where children with E1L also had low scores increasing the demands on the schools and their teachers. Children who had low initial scores made modest but significant progress during their reception year but failed to improve further during year 1 despite having non-verbal ability appropriate for their age. These results support previous findings that social deprivation can seriously delay language development, and that many children start school with weak communication skills. They add to previous findings by showing that the level of delay may differ substantially across schools in the same borough, by reporting data on children with EAL and by showing that children struggle to improve their abilities in the first 2 years of school

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries