Gene3D: modelling protein structure, function and evolution

The Gene3D release 4 database and web portal () provide a combined structural, functional and evolutionary view of the protein world. It is focussed on providing structural annotation for protein sequences without structural representatives—including the complete proteome sets of over 240 different species. The protein sequences have also been clustered into whole-chain families so as to aid functional prediction. The structural annotation is generated using HMM models based on the CATH domain families; CATH is a repository for manually deduced protein domains. Amongst the changes from the last publication are: the addition of over 100 genomes and the UniProt sequence database, domain data from Pfam, metabolic pathway and functional data from COGs, KEGG and GO, and protein–protein interaction data from MINT and BIND. The website has been rebuilt to allow more sophisticated querying and the data returned is presented in a clearer format with greater functionality. Furthermore, all data can be downloaded in a simple XML format, allowing users to carry out complex investigations at their own computers

The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis

The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath/) currently contains 43 229 domains classified into 1467 superfamilies and 5107 sequence families. Each structural family is expanded with sequence relatives from GenBank and completed genomes, using a variety of efficient sequence search protocols and reliable thresholds. This extended CATH protein family database contains 616 470 domain sequences classified into 23 876 sequence families. This results in the significant expansion of the CATHHMMmodel library to include models built from the CATH sequence relatives, giving a10%increase in coveragefor detecting remote homologues. An improved Dictionary of Homologous superfamilies (DHS) (http://www.biochem.ucl.ac.uk/bsm/dhs/) containing specific sequence, structural and functional information for each superfamily in CATH considerably assists manual validation of homologues. Information on sequence relatives in CATH superfamilies, GenBank and completed genomes is presented in the CATH associated DHS and Gene3D resources. Domain partnership information can be obtained from Gene3D (http://www.biochem.ucl.ac.uk/bsm/cath/Gene3D/). A new CATH server has been implemented (http://www.biochem.ucl.ac.uk/cgi-bin/cath/CathServer.pl) providing automatic classification of newly determined sequences and structures using a suite of rapid sequence and structure comparison methods. The statistical significance of matches is assessed and links are provided to the putative superfamily or fold group to which the query sequence or structure is assigned

The CATH domain structure database: new protocols and classification levels give a more comprehensive resource for exploring evolution

We report the latest release (version 3.0) of the CATH protein domain database (). There has been a 20% increase in the number of structural domains classified in CATH, up to 86 151 domains. Release 3.0 comprises 1110 fold groups and 2147 homologous superfamilies. To cope with the increases in diverse structural homologues being determined by the structural genomics initiatives, more sensitive methods have been developed for identifying boundaries in multi-domain proteins and for recognising homologues. The CATH classification update is now being driven by an integrated pipeline that links these automated procedures with validation steps, that have been made easier by the provision of information rich web pages summarising comparison scores and relevant links to external sites for each domain being classified. An analysis of the population of domains in the CATH hierarchy and several domain characteristics are presented for version 3.0. We also report an update of the CATH Dictionary of homologous structures (CATH-DHS) which now contains multiple structural alignments, consensus information and functional annotations for 1459 well populated superfamilies in CATH. CATH is directly linked to the Gene3D database which is a projection of CATH structural data onto ∼2 million sequences in completed genomes and UniProt

New developments in the InterPro database

InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (), and for download by anonymous FTP (). The InterProScan search tool is now also available via a web service at

A Unified View of Protein Sequence and Structure Using the Distributed Annotation System

The eFamily project aims to improve integration between protein sequence and structure data. One of the technologies being used to achieve this is the Distributed Annotation System (DAS). DAS is a specific Web service technology that performs the exchange of biological annotations. DAS is motivated by the idea that annotations should be provided by independent decentralised databases. Here, we describe DAS and compare it to other Web service technologies. We describe a registry server for DAS, and Spice

Effects of induced drought and tilting on biomass allocation, wood properties, compression wood formation and chemical composition of young Pinus radiata genotypes (clones)

Eight genotypes (clones) of Pinus radiata were subjected to drought and stem inclination to assess genotype response to common stressors. While drought stress reduced diameter growth, height growth and total biomass accumulation, root to shoot (R/S) ratios were unaffected. Drought-stressed plants had significantly lower average acoustic velocity, but longitudinal shrinkage (LS) and density were not different from those of the control plants. Radial diameter growth and R/S ratios were unaffected by tilting. Inclined stems had significantly lower acoustic velocity, and significantly higher LS and density than control stems. Acoustic velocity had a strong negative correlation with LS (r2=0.79). Compression wood (CW) content was much higher in tilted plants, compared to control and drought treatment plants. The CW of tilted trees had different chemistry than that of the CW of drought and control plants. Genotypes differed significantly in the amount of CW formed as a response to tilting, demonstrating that the formation and extent of CW is genetically influenced. Mechanical perturbation in conjunction with acoustic methods for assessing stiffness would be a useful approach for early-age selection of genotypes less prone to form CW

Frequency of five disease-causing genetic mutations in a large mixed-breed dog population (2011–2012)

<div><p>Background</p><p>A large and growing number of inherited genetic disease mutations are now known in the dog. Frequencies of these mutations are typically examined within the breed of discovery, possibly in related breeds, but nearly always in purebred dogs. No report to date has examined the frequencies of specific genetic disease mutations in a large population of mixed-breed dogs. Further, veterinarians and dog owners typically dismiss inherited/genetic diseases as possibilities for health problems in mixed-breed dogs, assuming hybrid vigor will guarantee that single-gene disease mutations are not a cause for concern. Therefore, the objective of this study was to screen a large mixed-breed canine population for the presence of mutant alleles associated with five autosomal recessive disorders: hyperuricosuria and hyperuricemia (HUU), cystinuria (CYST), factor VII deficiency (FVIID), myotonia congenita (MYC) and phosphofructokinase deficiency (PKFD). Genetic testing was performed in conjunction with breed determination via the commercially-available Wisdom Panel^TM test.</p><p>Results</p><p>From a population of nearly 35,000 dogs, homozygous mutant dogs were identified for HUU (n = 57) and FVIID (n = 65). Homozygotes for HUU and FVIID were identified even among dogs with highly mixed breed ancestry. Carriers were identified for all disorders except MYC. HUU and FVIID were of high enough frequency to merit consideration in any mixed-breed dog, while CYST, MYC, and PKFD are vanishingly rare.</p><p>Conclusions</p><p>The assumption that mixed-breed dogs do not suffer from single-gene genetic disorders is shown here to be false. Within the diseases examined, HUU and FVIID should remain on any practitioner’s rule-out list, when clinically appropriate, for all mixed-breed dogs, and judicious genetic testing should be performed for diagnosis or screening. Future testing of large mixed-breed dog populations that include additional known canine genetic mutations will refine our knowledge of which genetic diseases can strike mixed-breed dogs.</p></div

Validated constipation symptom and quality-of-life measures neither reflect patient and clinician concerns nor use words familiar to patients

© MA Healthcare Ltd. Patients' self-reported constipation symptoms, preferred terminology and quality of life (QoL) issues were explored through 14 semi-structured and five unstructured interviews. In a modified Delphi study, 11 clinicians rated the clinical importance of patient-reported symptoms and QoL issues. Results were compared with validated constipation assessment tools, using content and inductive thematic analysis methods. Three themes were identified: language describing constipation; symptoms and toilet behaviours; and QoL issues. Preferred terms for describing faeces and defecating were identified. Few of the 32 troublesome symptoms or QoL issues reported by participants appear in existing validated tools. All clinicians rated uncontrolled leakage of stool as clinically important, yet this is absent from assessment tools. It was concluded that present validated tools neither reflect patient concerns nor use language familiar to them, which may generate inaccurate assessment. A larger study may inform development of new patientreported outcome measures

Observed frequencies of alternate/mutated alleles by disorder in a large, mixed-breed canine population.

<p>Observed frequencies of alternate/mutated alleles by disorder in a large, mixed-breed canine population.</p