A strategy for finding regions of similarity in complete genome sequences

MOTIVATION: Complete genomic sequences will become available in the future. New methods to deal with very large sequences (sizes beyond 100 kb) efficiently are required. One of the main aims of such work is to increase our understanding of genome organization and evolution. This requires studies of the locations of regions of similarity. RESULTS: We present here a new tool, ASSIRC ('Accelerated Search for SImilarity Regions in Chromosomes'), for finding regions of similarity in genomic sequences. The method involves three steps: (i) identification of short exact chains of fixed size, called 'seeds', common to both sequences, using hashing functions; (ii) extension of these seeds into putative regions of similarity by a 'random walk' procedure; (iii) final selection of regions of similarity by assessing alignments of the putative sequences. We used simulations to estimate the proportion of regions of similarity not detected for particular region sizes, base identity proportions and seed sizes. This approach can be tailored to the user's specifications. We looked for regions of similarity between two yeast chromosomes (V and IX). The efficiency of the approach was compared to those of conventional programs BLAST and FASTA, by assessing CPU time required and the regions of similarity found for the same data set. AVAILABILITY: Source programs are freely available at the following address: ftp://ftp.biologie.ens. fr/pub/molbio/assirc.tar.gz CONTACT: vincens@biologie.ens.fr, hazout@urbb.jussieu.fr      

Genetic identity and differential gene expression between Trichomonas vaginalis and Trichomonas tenax

Background  

Trichomonas vaginalis is a human urogenital pathogen responsible for trichomonosis, the number-one, non-viral sexually transmitted disease (STD) worldwide, while T. tenax is a commensal of the human oral cavity, found particularly in patients with poor oral hygiene and advanced periodontal disease. The extent of genetic identity between T. vaginalis and its oral commensal counterpart is unknown.     

The Drosophila SHC adaptor protein is required for signaling by a subset of receptor tyrosine kinases

Receptor tyrosine kinases (RTKs) transduce signals via cytoplasmic adaptor proteins to downstream signaling components. We have identified loss-of-function mutations in dshc, the Drosophila homolog of the mammalian adaptor protein SHC. A point mutation in the phosphotyrosine binding (PTB) domain completely abolishes DSHC function and provides in vivo evidence for the function of PTB domains. Unlike other adaptor proteins, DSHC is involved in signaling by only a subset of RTKs: dshc mutants show defects in Torso and DER but not Sevenless signaling, which is confirmed by epistasis experiments. We show by double-mutant analysis that the adaptors DOS, DRK, and DSHC act in parallel to transduce the Torso signal. Our results suggest that DSHC confers specificity to receptor signaling.     

Patients' and practitioners' views of knee osteoarthritis and its management: a qualitative interview study

Purpose

To identify the views of patients and care providers regarding the management of knee osteoarthritis (OA) and to reveal potential obstacles to improving health care strategies.

Methods

We performed a qualitative study based on semi-structured interviews of a stratified sample of 81 patients (59 women) and 29 practitioners (8 women, 11 general practitioners [GPs], 6 rheumatologists, 4 orthopedic surgeons, and 8 [4 GPs] delivering alternative medicine).

Results

Two main domains of patient views were identified: one about the patient–physician relationship and the other about treatments. Patients feel that their complaints are not taken seriously. They also feel that practitioners act as technicians, paying more attention to the knee than to the individual, and they consider that not enough time is spent on information and counseling. They have negative perceptions of drugs and a feeling of medical uncertainty about OA, which leads to less compliance with treatment and a switch to alternative medicine. Patients believe that knee OA is an inevitable illness associated with age, that not much can be done to modify its evolution, that treatments are of little help, and that practitioners have not much to propose. They express unrealistic fears about the impact of knee OA on daily and social life. Practitioners'' views differ from those of patients. Physicians emphasize the difficulty in elaborating treatment strategies and the need for a tool to help in treatment choice.

Conclusions

This qualitative study suggests several ways to improve the patient–practitioner relationship and the efficacy of treatment strategies, by increasing their acceptability and compliance. Providing adapted and formalized information to patients, adopting more global assessment and therapeutic approaches, and dealing more accurately with patients'' paradoxal representation of drug therapy are main factors of improvement that should be addressed.     

Strategic emphases for tropical diseases research: a TDR perspective

Setting priorities for health research is a difficult task, especially for the neglected diseases of the poor. A new approach to priority setting for tropical diseases research has been adopted by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (known as the TDR). Priorities are defined on the basis of a comprehensive analysis of research needs and research opportunities for each of the ten major tropical diseases in the TDR portfolio. The resulting strategic emphases matrix reflects the priorities for tropical diseases research from the perspective of the TDR. Its purpose is not to impose global research priorities, but we believe the results could be useful to other organizations.     

SKPDB: a structural database of shikimate pathway enzymes

Background  

The functional and structural characterisation of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design. The main interest in studying shikimate pathway enzymes involves the fact that they are essential for bacteria but do not occur in humans, making them selective targets for design of drugs that do not directly impact humans.