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Biomedical subjects

M Senger

Publications and source records attributed to M Senger.

9 recordsLinked to original sources

SOAP-based services provided by the European Bioinformatics Institute.

SOAP (Simple Object Access Protocol) (http://www.w3.org/TR/soap) based Web Services technology (http://www.w3.org/ws) has gained much attention as an open standard enabling interoperability among applications across heterogeneous architectures and different networks. The European Bioinformatics Institute (EBI) is using this technology to provide robust data retrieval and data analysis mechanisms to the scientific community and to enhance utilization of the biological resources it already provides [N. Harte, V. Silventoinen, E. Quevillon, S. Robinson, K. Kallio, X. Fustero, P. Patel, P. Jokinen and R. Lopez (2004) Nucleic Acids Res., 32, 3-9]. These services are available free to all users from http://www.ebi.ac.uk/Tools/webservices.

Biotechnology↗

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients.

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age +/- SD: 51.3 +/- 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

Adult↗

Exploring Williams-Beuren syndrome using myGrid.

MOTIVATION: In silico experiments necessitate the virtual organization of people, data, tools and machines. The scientific process also necessitates an awareness of the experience base, both of personal data as well as the wider context of work. The management of all these data and the co-ordination of resources to manage such virtual organizations and the data surrounding them needs significant computational infra-structure support. RESULTS: In this paper, we show that (my)Grid, middleware for the Semantic Grid, enables biologists to perform and manage in silico experiments, then explore and exploit the results of their experiments. We demonstrate (my)Grid in the context of a series of bioinformatics experiments focused on a 1.5 Mb region on chromosome 7 which is deleted in Williams-Beuren syndrome (WBS). Due to the highly repetitive nature of sequence flanking/in the WBS critical region (WBSCR), sequencing of the region is incomplete leaving documented gaps in the released sequence. (my)Grid was used in a series of experiments to find newly sequenced human genomic DNA clones that extended into these 'gap' regions in order to produce a complete and accurate map of the WBSCR. Once placed in this region, these DNA sequences were analysed with a battery of prediction tools in order to locate putative genes and regulatory elements possibly implicated in the disorder. Finally, any genes discovered were submitted to a range of standard bioinformatics tools for their characterization. We report how (my)Grid has been used to create workflows for these in silico experiments, run those workflows regularly and notify the biologist when new DNA and genes are discovered. The (my)Grid services collect and co-ordinate data inputs and outputs for the experiment, as well as much provenance information about the performance of experiments on WBS. AVAILABILITY: The (my)Grid software is available via http://www.mygrid.org.uk

Algorithms↗

Four years of experience with silver-copper ionization for control of legionella in a german university hospital hot water plumbing system.

Silver-copper ionization was used for controlling Legionella distribution in a German university hospital hot water plumbing system for 4 years. In the beginning, silver concentrations were not allowed to exceed 10 microg/L because of drinking water regulation limits in Germany. Water samples were monitored for Legionella counts, temperature, and silver and copper concentrations. A significant (P<.001) 3.8-log reduction of Legionella counts, from 40, 000 cfu/L to 7 cfu/L, was found during the first year with silver-copper ionization. Nevertheless, the long-term efficacy of silver concentrations <10 ,++microg/L was not sufficient. Legionella counts increased to 10,000 cfu/L during the third year. During the fourth year, we studied the influence of higher silver concentrations on Legionella distribution. With an average silver level of 30 microg/L, only a 1.3-log reduction in Legionella, to 500 cfu/L, was achieved. The effect was not significant (P=.071); therefore, it must be considered that Legionella developed a tolerance to silver ions.

Chlorine↗

W2H: WWW interface to the GCG sequence analysis package.

MOTIVATION: The user-friendly, graphical X-windows interface (WPI) to the GCG sequence analysis package can often not be used due to the lack of an X-server on PC or Macintosh computers. Because Web browsers like Netscape are much more common on those platforms, we decided to develop W2H, a WWW interface to the GCG Sequence Analysis Software Package with nearly the same functionality as the X-windows interface WPI. RESULTS: The new WWW interface (W2H) to the GCG Sequence Analysis Software Package (Wisconsin Package) supports modern Web technologies, like client-pull method, or embedded scripting language, and provides a reasonable platform independence. The interface is quite comprehensive with advanced features like sequence selector, search set builder, enzyme chooser, access to sequence databases, uploading client files to the GCG server or displaying and manipulating graphical outputs in addition to GCG analysis programs. W2H also manages secure access to both GCG server and user data. For special environments, like workshops, conferences and company intranets, there is a special mode (Intranet mode) with less security constraints. The behaviour of W2H is mostly controlled by meta-data files describing the applications and giving a base for dynamic creation of HTML documents. This paper presents mainly the development approaches used, and architectural design aspects of W2H. AVAILABILITY: W2H is available by ftp://ftp.ebi.ac. uk/pub/software/unix/w2h or ftp://genome.dkfz-heidelberg.de/pub/w2h CONTACT: m.senger@ebi.ac.uk

Computational Biology↗

[Effect of silver and copper ions on survival of Legionella pneumophila in tap water].

In vitro studies were performed to give information about the required metal concentrations in decontaminating Legionella-loaded warm water systems with the electrochemical generation of Ag+ and Cu2+ ions. The influence of Ag and Cu ions, as single compounds and in combination, on the survival of Legionella pneumophila (serogroup 6) was determined in tap water at 45 degrees C. Marked differences were detected in the action of these metals. Ag produced a much stronger inhibition than Cu. No additive effect was demonstrated when using Ag/Cu-combinations in the ratio of 1:10. In this case only the Ag-induced inhibition was detected. After 1 h of incubation at 45 degrees C a concentration of 80 + 800 micrograms/L Ag + Cu was needed to produce the maximal inhibitory effect (a 5 log decrease). An identical effect was seen after exposure to 20 + 200 micrograms/L Ag + Cu in the long-term action (24 h of incubation). The minimum inhibitory concentration after long-term incubation was 5 + 50 micrograms/L Ag + Cu. These metal concentrations produced a 1 log reduction. The in vitro results are discussed under consideration of earlier investigations after metering Ag and Cu into a Legionella-loaded water system and generated the following conclusions: In the beginning highly contaminated water systems at 45 degrees C need concentrations between 40 and 80 micrograms/L Ag + 400 to 800 micrograms/L Cu to kill Legionellas. After effective reduction of Legionella concentration of at least some logarithmic powers a slow constant maintenance concentration of 5 to 20 micrograms/L Ag + 50 to 200 micrograms/L Cu could be applied. At 22 degrees C the in vitro inactivation response is much lower. On the other hand in warm water systems with temperatures of 50 to 60 degrees C lower metal concentrations are sufficient.

Bacteriological Techniques↗

X-HUSAR, an X-based graphical interface for the analysis of genomic sequences.

Management and analysis of nucleotide and protein sequence and structure data constitute a traditional area of bioinformatics. Since the analytical programs are frequently developed by researchers, rather than software engineers, they tend to suffer from idiosyncratic and non-ergonomic man-machine interfaces. We report on HUSAR, our 140+ collection of third-party, as well as in-house developed or adapted, sequence manipulation and analysis tools, well integrated into the UNIX operating system environment and accessible via consistent menu-aware interface. Most of the HUSAR programs can be completely specified by UNIX command-line options; they can thus be run in batches or combined into pipes. Adding such a program into the HUSAR environment is almost a 'plug-and-play' exercise. HUSAR has been recently complemented with a graphical client interface, X-HUSAR, to support users on UNIX platforms with X11 windowing systems. The whole X-HUSAR interface is based on a single generic program, COMLIGEN, and a number of specific configuration files. COMLIGEN interprets those files and renders appropriate windows, menus, and other interactive elements, which help the end user in selecting application programs and specifying their options. Efforts of extending both HUSAR and X-HUSAR are roughly linear to the size of the collection.

Animals↗

Thyrotropin and prolactin responses to thyrotropin-releasing hormone in young men at high or low risk for alcoholism.

A reduced thyrotropin (TSH) response to TSH-releasing hormone (TRH) has been reported in a portion of abstinent alcoholic men without evidence of cirrhosis of the liver. It is not known whether this neuroendocrine change is a precursor of alcoholism or a sequelae of heavy alcohol consumption. Three of four published studies have found evidence for differences in TRH-induced TSH response in subjects at high risk for alcoholism, based on family history, compared with subjects at low risk for alcoholism. To test further the hypothesis that the TRH-induced TSH response is a vulnerability marker for alcoholism, we tested 25 young men with an alcoholic father [family history-positive (FHP)] and matched them, on alcohol consumption, to 25 young men with no identified first- or second-degree relatives with alcoholism [family history-negative (FHN)]. FHP subjects were further categorized based on whether their father had shown signs of alcohol problems before age 25 years (FHP-Early, n = 10) or after age 24 years (FHP-Late, n = 12). FHP subjects did not differ from FHN subjects in their baseline levels of thyroid hormones, glucose, cortisol, or TSH. However, the distribution of TSH responses in the FHP subjects was skewed toward lower values, compared with FHN subjects (p = 0.12). Furthermore, FHP-Late subjects had lower TSH responses than FHN subjects (p = 0.02), whereas the TSH response of FHP-Early subjects was not different from FHN subjects. Prolactin responses to TRH were similar across all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prototype implementation of the integrated genomic database.

We aim to develop an open software system to handle human genome data. The system, called Integrated Genomic Database (IGD), will integrate information from many genomic databases and experimental resources into a comprehensive target-end database (IGD TED). Users will access front-end client systems (IGD FRED) to download data of interest to their computers and merge them with their own local data. FREDs will provide persistent storage of, and instant access to, retrieved data; a friendly graphical interface; tools for querying, browsing, analyzing, and editing local data; interface to external analysis; and tools for communicating with the outside world. The TED will be accessible over the network (online and offline) as a read-only resource for multiple clients. It collects data from major databases for nucleotide and protein sequences and structures, genome maps, experimental reagents, phenotypes, and bibliographic data, and sets of raw data produced at genome centers and laboratories. Beside character-based access via Gopher, WAIS, FTP, and several query language interfaces to the TED, we will develop a specialized front-end client, IGD FRED, with its own database manager, based on the ACEDB program. The FRED will support graphical display methods for sequence feature maps, chromosomal genetic and physical maps, and experimental objects like clone grids, etc. FRED will also provide an interface to important analysis software packages and tools for submitting data to external databases in their own format.

Computer Communication Networks↗