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PubMed2005

PATIKAweb: a Web interface for analyzing biological pathways through advanced querying and visualization.

Patikaweb provides a Web interface for retrieving and analyzing biological pathways in the Patika database, which contains data integrated from various prominent public pathway databases. It features a user-friendly interface, dynamic visualization and automated layout, advanced graph-theoretic queries for extracting biologically important phenomena, local persistence capability and exporting facilities to various pathway exchange formats.

Computer Graphics↗

PubMed2006

PIANA: protein interactions and network analysis.

UNLABELLED: We present a software framework and tool called Protein Interactions And Network Analysis (PIANA) that facilitates working with protein interaction networks by (1) integrating data from multiple sources, (2) providing a library that handles graph-related tasks and (3) automating the analysis of protein-protein interaction networks. PIANA can also be used as a stand-alone application to create protein interaction networks and perform tasks such as predicting protein interactions and helping to identify spots in a 2D electrophoresis gel. AVAILABILITY: PIANA is under the GNU GPL. Source code, database and detailed documentation may be freely downloaded from http://sbi.imim.es/piana.

Computer Graphics↗

PubMed2002

A molecular cytogenetic map of sorghum chromosome 1. Fluorescence in situ hybridization analysis with mapped bacterial artificial chromosomes.

We used structural genomic resources for Sorghum bicolor (L.) Moench to target and develop multiple molecular cytogenetic probes that would provide extensive coverage for a specific chromosome of sorghum. Bacterial artificial chromosome (BAC) clones containing molecular markers mapped across sorghum linkage group A were labeled as probes for fluorescence in situ hybridization (FISH). Signals from single-, dual-, and multiprobe BAC-FISH to spreads of mitotic chromosomes and pachytene bivalents were associated with the largest sorghum chromosome, which bears the nucleolus organizing region (NOR). The order of individual BAC-FISH loci along the chromosome was fully concordant to that of marker loci along the linkage map. In addition, the order of several tightly linked molecular markers was clarified by FISH analysis. The FISH results indicate that markers from the linkage map positions 0.0-81.8 cM reside in the short arm of chromosome 1 whereas markers from 81.8-242.9 cM are located in the long arm of chromosome 1. The centromere and NOR were located in a large heterochromatic region that spans approximately 60% of chromosome 1. In contrast, this region represents only 0.7% of the total genetic map distance of this chromosome. Variation in recombination frequency among euchromatic chromosomal regions also was apparent. The integrated data underscore the value of cytological data, because minor errors and uncertainties in linkage maps can involve huge physical regions. The successful development of multiprobe FISH cocktails suggests that it is feasible to develop chromosome-specific "paints" from genomic resources rather than flow sorting or microdissection and that when applied to pachytene chromatin, such cocktails provide an especially powerful framework for mapping. Such a molecular cytogenetic infrastructure would be inherently cross-linked with other genomic tools and thereby establish a cytogenomics system with extensive utility in development and application of genomic resources, cloning, transgene localization, development of plant "chromonomics," germplasm introgression, and marker-assisted breeding. In combination with previously reported work, the results indicate that a sorghum cytogenomics system would be partially applicable to other gramineous genera.

Chromosome Mapping↗

PubMed2006

Validating the theoretical structure of the Treatment Self-Regulation Questionnaire (TSRQ) across three different health behaviors.

Nearly 40% of mortality in the United States is linked to social and behavioral factors such as smoking, diet and sedentary lifestyle. Autonomous self-regulation of health-related behaviors is thus an important aspect of human behavior to assess. In 1997, the Behavior Change Consortium (BCC) was formed. Within the BCC, seven health behaviors, 18 theoretical models, five intervention settings and 26 mediating variables were studied across diverse populations. One of the measures included across settings and health behaviors was the Treatment Self-Regulation Questionnaire (TSRQ). The purpose of the present study was to examine the validity of the TSRQ across settings and health behaviors (tobacco, diet and exercise). The TSRQ is composed of subscales assessing different forms of motivation: amotivation, external, introjection, identification and integration. Data were obtained from four different sites and a total of 2731 participants completed the TSRQ. Invariance analyses support the validity of the TSRQ across all four sites and all three health behaviors. Overall, the internal consistency of each subscale was acceptable (most alpha values >0.73). The present study provides further evidence of the validity of the TSRQ and its usefulness as an assessment tool across various settings and for different health behaviors.

Adolescent↗

PubMed1997

Cryopreservation: the practicalities of evaluation.

An attempt was made to integrate data from cryopreserved embryos with those from fresh embryos to obtain a realistic assessment of the role of cryopreservation in assisted reproductive treatment. Principles were applied to previously published data from a large prospective randomized multicentre study comprising recombinant and urinary follicle stimulating hormone in in-vitro fertilization.

Cryopreservation↗

PubMed2005

Years of life lost attributable to air pollution in Switzerland: dynamic exposure-response model.

BACKGROUND: There is debate on how the effect of air pollution should be assessed. We propose an approach to estimate its impact on adult and infant mortality that integrates data from long-term epidemiological studies and studies of interventions to reduce pollution. We use the method to estimate the number of years of life lost (YLLs) attributable to air pollution during 1 year in Switzerland. METHODS: A dynamic exposure-response model was implemented, which uses an exponential function (exp(-kt)) to model the change in mortality after cessation of air pollution. The model was populated with relative risk estimates and estimates of time constant k from the literature. Air pollution exposure in Switzerland was modelled using data from emission inventories. YLLs attributable to air pollution were calculated by taking the difference between observed survival probabilities in Switzerland in 2000 and modified survival probabilities, assuming no air pollution during the year 2000. RESULTS: Meta-analyses of three studies of adult mortality and five studies of infant mortality gave relative risks of 1.059 (95% confidence interval (CI) 1.031-1.088) and 1.056 (95% CI 1.026-1.088) per 10 mug/m(3) increase in PM10 concentration. Time constants k derived from two studies of the effects of the closing down of a steel mill in the Utah Valley and of the coal ban in Dublin were 0.88 and 0.11. Assuming a time constant k of 0.5 resulted in 42 400 (95% CI 22 600-63 600) YLLs, with 4.0% being ascribed to infant deaths. A total of 39% of the effect occurred in the same year and 80% within 5 years. The estimated number of YLLs was little affected by the choice of the time constant. CONCLUSIONS: In contrast to traditional steady-state models the dynamic model allows changes in mortality following short-term increases or decreases in air pollution levels to be quantified. This type of information is of obvious interest to policy makers.

Adult↗

PubMed2001

HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae.

An experimental Streptococcus pneumoniae pneumonia model in rabbits was used to assess the efficacy of amoxycillin, erythromycin and a new ketolide, telithromycin (HMR 3647). The MICs of amoxycillin, erythromycin and HMR 3647 for the three clinical S. pneumoniae strains used were, respectively, (mg/L): 0.01, 16 and 0.02 (strain 195); 2, 0.25 and 0.02 (strain 16089); 8, >64 and 0.02 (strain 11724). Antibiotic therapy reproduced human serum pharmacokinetics (amoxycillin 1 g iv tds or erythromycin 500 mg qds or HMR 3647 800 mg bd). Forty-eight hours of therapy with HMR 3647 and amoxycillin resulted in significant bacterial clearance in the lungs and spleen of rabbits infected by S. pneumoniae strain 195 and strain 16089 (at least 3 log(10) cfu/g decrease, P < 0.001). Erythromycin was active against only the erythromycinsusceptible strain (3 log(10) cfu/g decrease at 48 h, P < 0.001). None of the antibiotics showed significant efficacy with strain 11724. All agents produced significant bacterial clearance when time above MBC was >33%, and microbiological failure when it was <25%, whereas MIC was not correlated with microbiological outcome with HMR 3647. Our findings suggest that pharmacodynamic data integrating MBC may be predictive of microbiological success or failure with greater accuracy than with MIC. HMR 3647 produced significant bacterial clearance in both penicillin- and erythromycin-resistant pneumonia, but was less effective against the highly erythromycin-resistant S. pneumoniae strain.

Amoxicillin↗

PubMed2026

Immature Neutrophil Programs Associate With Burn Mortality and Extend Across Critical Illnesses.

Severe burns provoke a systemic "genomic storm," yet cell states associated with divergent outcomes remain unclear. We profiled blood cells by single-cell RNA-Sequencing (73 014 cells) from adult patients with burn injuries within postburn day 17 (n = 4) and healthy donors (n = 5), integrated data with bulk signatures of burn size, inhalation injury, and mortality, and evaluated clinical associations in the American Burn Association National Burn Repository. Burn was associated with emergency hematopoiesis marked by expansion of hematopoietic stem/progenitor-like cells, immature neutrophils, and plasmablast/plasma cell states, alongside depletion of naïve CD4+/CD8+ T cells and dendritic cells. Larger burns (>20% TBSA) showed enrichment of humoral transcriptional programs, including plasmablast/plasma cell activation and suppression of cytotoxic CD8+ T-cell states. In multivariable models, inhalation injury was a stronger predictor of death (adjusted odds ratio [OR] 1.9) than burn size (adjusted OR 1.1) and shared greater overlap with the most perturbed single cells in non-survivors; 55% of co-perturbed cells were neutrophils, implicating granulocyte dysregulation as a common lethal axis. We identified a neutrophil-specific 5-gene panel (OLFM4, RETN, LCN2, ARG1, and BTNL3) that discriminated survivors vs non-survivors after burns (area under the curve [AUC] > 0.9) and generalized to trauma (n = 158; AUC 0.81) and intensive care unit COVID-19 (n = 103; AUC 0.75), providing information orthogonal to conventional biomarkers and severity scores. Cytomorphology corroborated transcriptomic immaturity, with ~2-fold higher band neutrophils and larger neutrophil size in a fatal case. Computational drug-reversal analysis highlighted galectin-1 inhibition as a candidate modulator of mortality-associated neutrophil programs. Together, our findings suggest that immature neutrophils represent a shared immune feature across severe burns and other forms of critical illness.

Humans↗

PubMed2006

The lung cancer database project at the National Cancer Center, Japan: study design, corresponding rate and profiles of cohort.

BACKGROUND: The lung cancer database project was established in 1999 at the National Cancer Center Hospital East, Japan, as an ongoing project to integrate data on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future. METHODS: Between July 1999 and July 2004, consecutive lung cancer patients were recruited into this project. The baseline survey consisted of self-administered questionnaires concerning various demographic data, health habits and psychological factors. Medical information was obtained from the patients' medical charts. Urine specimens and blood samples were collected, and DNA was extracted from blood lymphocytes. RESULTS: Out of the 2506 patients who were asked to participate in the project, 2036 (81%) patients with newly diagnosed, untreated primary lung cancer were enrolled. The final analytic cohort consisted of 1995 patients. Virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively. In a follow-up survey conducted to determine vital status as of December 2004, a total of 1051 patients (53%) had died and 44 patients (2%) were lost to follow-up. CONCLUSIONS: This paper overviews the rationale for initiating the lung cancer database project, Japan. This database should prove useful for researchers examining the pathogenesis of lung cancer and may contribute to the formulation of a framework for cancer treatment.

Adult↗

PubMed2003

Using quaternary structures to assess the evolutionary history of proteins: the case of the aspartate carbamoyltransferase.

Many evolutionary scenarios describing the history of proteins are based solely on phylogenetic studies. We have designed a new approach that allows ascertainment of such questionable scenarios by taking into account quaternary structures: we used aspartate carbamoyltransferase (ATCase) as a case study. Prokaryotic ATCases correspond to different classes of quaternary structures according to the mode of association of the catalytic PyrB subunit with other polypeptides, either the PyrI regulatory subunit (class B) or a dihydroorotase (class A), which may be active (PyrC, subclass A1) or inactive (PyrC', subclass A2). Class C is uniquely made up of trimers of PyrB. The PyrB phylogenetic tree is not congruent with the tree of life, but it became coherent when we recognized the existence of two families of ATCases, ATC I and ATC II. Remarkably, a very strong correlation was found between the pattern of PyrB phylogenetic clustering and the different classes of quaternary structures of ATCases. All class B ATCases form a clade in family ATC II, which also contains all eukaryotic sequences. In contrast, family ATC I is made up of classes A and C. These results suggest unexpected common ancestry for prokaryotic B and eukaryotic ATCases on the one hand, and for A and C on the other. Thus, the emergence of specific quaternary structures appears to have been a more recent event than the separation into the ATC I and ATC II families. We propose that different evolutionary constraints, depending on the identity of the partners interacting in the different kinds of holoenzymes, operated in a concerted way on the ancestral pyrB genes and the respective associated genes pyrI or pyrC, so as to maintain appropriate inter-polypeptides interactions at the level of quaternary structure. The process of coevolution of genes encoding proteins interacting in various holoenzymes has been assessed by calculating the correlation coefficient between their respective phylogenetic trees. Our approach integrating data obtained from the separate fields of structural biology and molecular evolution could be useful in other cases where pure statistical data need to receive independent confirmation.

Archaea↗

PubMed2001

The MetaFam Server: a comprehensive protein family resource.

MetaFam is a comprehensive relational database of protein family information. This web-accessible resource integrates data from several primary sequence and secondary protein family databases. By pooling together the information from these disparate sources, MetaFam is able to provide the most complete protein family sets available. Users are able to explore the interrelationships among these primary and secondary databases using a powerful graphical visualization tool, MetaFamView. Additionally, users can identify corresponding sequence entries among the sequence databases, obtain a quick summary of corresponding families (and their sequence members) among the family databases, and even attempt to classify their own unassigned sequences. Hypertext links to the appropriate source databases are provided at every level of navigation. Global family database statistics and information are also provided. Public access to the data is available at http://metafam.ahc.umn.edu/.

Computational Biology↗

PubMed2003

The pre-ribosomal network.

Recent achievements in yeast functional proteomics have significantly advanced our knowledge about ribosome biogenesis. Here, we present a program developed to integrate data from various proteome analyses with cell biological data on components present in the ribosome producing factories. This program allows users to attribute factors to certain complexes and to specific steps of ribosome biogenesis. Thus, it helps to gain novel insights into the complex network involved in maturation of ribosomal subunits. The database can be accessed at the URL http://www.pre-ribosome.de.

Biomarkers↗

PubMed2003

DNannotator: Annotation software tool kit for regional genomic sequences.

Sequence annotation is essential for genomics-based research. Investigators of a specific genomic region who have developed abundant local discoveries such as genes and genetic markers, or have collected annotations from multiple resources, can be overwhelmed by the difficulty in creating local annotation and the complexity of integrating all the annotations. Presenting such integrated data in a form suitable for data mining and high-throughput experimental design is even more daunting. DNannotator, a web application, was designed to perform batch annotation on a sizeable genomic region. It takes annotation source data, such as SNPs, genes, primers, and so on, prepared by the end-user and/or a specified target of genomic DNA, and performs de novo annotation. DNannotator can also robustly migrate existing annotations in GenBank format from one sequence to another. Annotation results are provided in GenBank format and in tab-delimited text, which can be imported and managed in a database or spreadsheet and combined with existing annotation as desired. Graphic viewers, such as Genome Browser or Artemis, can display the annotation results. Reference data (reports on the process) facilitating the user's evaluation of annotation quality are optionally provided. DNannotator can be accessed at http://sky.bsd.uchicago.edu/DNannotator.htm.

Chromosomes, Human, Pair 13↗

PubMed2006

POGs/PlantRBP: a resource for comparative genomics in plants.

POGs/PlantRBP (http://plantrbp.uoregon.edu/) is a relational database that integrates data from rice, Arabidopsis, and maize by placing the complete Arabidopsis and rice proteomes and available maize sequences into 'putative orthologous groups' (POGs). Annotation efforts will focus on predicted RNA binding proteins (RBPs): i.e. those with known RNA binding domains or otherwise implicated in RNA function. POGs form the heart of the database, and were assigned using a mutual-best-hit-strategy after performing BLAST comparisons of the predicted Arabidopsis and rice proteomes. Each POG entry includes orthologs in Arabidopsis and rice, annotated with domain organization, gene models, phylogenetic trees, and multiple intracellular targeting predictions. A graphical display maps maize sequences on to their most similar rice gene model. The database can be queried using any combination of gene name, accession, domain, and predicted intracellular location, or using BLAST. Useful features of the database include the ability to search for proteins with both a specified domain content and intracellular location, the concurrent display of mutual best hits and phylogenetic trees which facilitates evaluation of POG assignments, the association of maize sequences with POGs, and the display of targeting predictions and domain organization for all POG members, which reveals consistency, or lack thereof, of those predictions.

Amino Acid Sequence↗

PubMed1996

Stages of future technological developments in haemodialysis.

Understanding the needs of the patients, dialysis staff, and nephrologists is the first logical step in the technological development of better haemodialysis devices. This includes the understanding of large and small uraemic toxins and their removal by dialysis membranes, pathophysiology of intradialytic symptomatology, and problems associated with vascular access. Each of these areas can benefit from profiling techniques. Profiling of urea (urea kinetics), solute clearance profiles of dialysis membranes, and volume profiling are areas that are undergoing active investigations and incorporation into clinical practice. Volume profiling currently entails the monitoring of intravascular and total body fluids as well as the measurement of vascular access flow. Development of sophisticated software is necessary to integrate data from various profiling techniques into dialysis equipment in a meaningful manner in order to optimize the dialysis treatment. The ultimate benefits of these devices should take into account the medical, psychosocial, and financial aspects of various parties involved.

Algorithms↗

PubMed1990

Neurobehavioral studies in schizophrenia: implications for regional brain dysfunction.

The application of neurobehavioral methods to the study of brain function in schizophrenia can provide useful information on the neurobiology of schizophrenia. Standard neuropsychological batteries were designed to assess behavioral correlates of regional brain function. Methodological considerations in the application of these tests to schizophrenia are discussed. Although there is considerable evidence for both frontal and temporal lobe dysfunction in schizophrenia, the field is likely to advance further through the systematic study of brain function. A combination of neurobehavioral and physiological data obtained simultaneously is a promising avenue to pursue, and the behavioral imaging method is presented as an example of one approach to data integration.

Algorithms↗

PubMed2004

Progress in the clinical development of new marine-derived anticancer compounds.

Naturally derived anticancer agents continue to be instrumental in the systemic therapeutic intervention against solid tumors and hematological malignancies. Such compounds now have a relevant role in contemporary models of combination with targeted agents, thus providing a rationale to consider nature as a valid tool to discover new innovative anticancer agents. The marine ecosystem has increasingly been the focus of interest for new discoveries in the field that are expected to be of significant therapeutic impact in cancer patients. A critical review of the integrated data generated in our marine-derived anticancer program seems to confirm such expentancies. ET-743 (Yondelis) represents the first new agent developed against advanced pretreated soft tissue sarcoma in the past 25 years, and also harbors activity in women bearing pretreated ovarian cancer and a solid potential in combination therapy. The lack of cumulative toxicities makes this compound suitable for long-lasting therapies, reversible transaminitis being the most prevalent toxicity. Aplidin has shown a positive therapeutic index in phase I trials and phase II studies are ongoing. In contrast to the lack of bone marrow toxicity, a set of translational results anticipates a potential in leukemia. Kahalalide F has also successfully completed the phase I program in solid tumors with evidence of activity in resistant tumors and phase II studies are under way. Finally, the mechanistic data generated in parallel with the clinical program confirms the potential of the marine ecosystem in the discovery of new agents acting against new cellular targets of relevance in cancer cell biology.

Antineoplastic Agents↗

PubMed1993

The variability of processing of technetium-99m DTPA renography. Role of interpolative background subtraction.

In quantitative renography, observer-dependent selection of renal outlines and background regions may account for considerable variability. This study of differential renal function with Tc-99m DTPA scintigraphy compares interpolative background subtraction with the authors' routine techniques; the latter involves background-subtracted uptake on data integrated over 1-3 minutes after injection. Other techniques considered were omission of background subtraction and use of 1-2 minute integration. The normal range was established in 24 hypertensive patients who had a normal angiogram and a normal radiometric glomerular filtration rate. The test set of 52 other hypertensive patients included 27 with renal artery stenosis. All techniques correlated well with the routine method (r > or = 0.98); however the interpolative background technique was unique in preserving the depiction of renal asymmetry but reducing the variability of replicate measurements (P < 0.05). Reduced renal function increased the variability of routine measurements, but the interpolative background subtraction method performed better in this instance (P < 0.01). Thus, the new technique appears to improve the definition of renal outlines and increase the reliability of measurements of differential renal function.

Algorithms↗