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PubMed2004

A collection of 11 800 single-copy Ds transposon insertion lines in Arabidopsis.

More than 10 000 transposon-tagged lines were constructed by using the Activator (Ac)/Dissociation (Ds) system in order to collect insertional mutants as a useful resource for functional genomics of Arabidopsis. The flanking sequences of the Ds element in the 11 800 independent lines were determined by high-throughput analysis using a semi-automated method. The sequence data allowed us to map the unique insertion site on the Arabidopsis genome in each line. The Ds element of 7566 lines is inserted in or close to coding regions, potentially affecting the function of 5031 of 25 000 Arabidopsis genes. Half of the lines have Ds insertions on chromosome 1 (Chr. 1), in which donor lines have a donor site. In the other half, the Ds insertions are distributed throughout the other four chromosomes. The intrachromosomal distribution of Ds insertions varies with the donor lines. We found that there are hot spots for Ds transposition near the ends of every chromosome, and we found some statistical preference for Ds insertion targets at the nucleotide level. On the basis of systematic analysis of the Ds insertion sites in the 11 800 lines, we propose the use of Ds-tagged lines with a single insertion in annotated genes for systematic analysis of phenotypes (phenome analysis) in functional genomics. We have opened a searchable database of the insertion-site sequences and mutated genes (http://rarge.gsc.riken.go.jp/) and are depositing these lines in the RIKEN BioResource Center as available resources (http://www.brc.riken.go.jp/Eng/).

Arabidopsis↗
PubMed2006

A new experimental approach for studying bacterial genomic island evolution identifies island genes with bacterial host-specific expression patterns.

BACKGROUND: Genomic islands are regions of bacterial genomes that have been acquired by horizontal transfer and often contain blocks of genes that function together for specific processes. Recently, it has become clear that the impact of genomic islands on the evolution of different bacterial species is significant and represents a major force in establishing bacterial genomic variation. However, the study of genomic island evolution has been mostly performed at the sequence level using computer software or hybridization analysis to compare different bacterial genomic sequences. We describe here a novel experimental approach to study the evolution of species-specific bacterial genomic islands that identifies island genes that have evolved in such a way that they are differentially-expressed depending on the bacterial host background into which they are transferred. RESULTS: We demonstrate this approach by using a "test" genomic island that we have cloned from the Salmonella typhimurium genome (island 4305) and transferred to a range of Gram negative bacterial hosts of differing evolutionary relationships to S. typhimurium. Systematic analysis of the expression of the island genes in the different hosts compared to proper controls allowed identification of genes with genera-specific expression patterns. The data from the analysis can be arranged in a matrix to give an expression "array" of the island genes in the different bacterial backgrounds. A conserved 19-bp DNA site was found upstream of at least two of the differentially-expressed island genes. To our knowledge, this is the first systematic analysis of horizontally-transferred genomic island gene expression in a broad range of Gram negative hosts. We also present evidence in this study that the IS200 element found in island 4305 in S. typhimurium strain LT2 was inserted after the island had already been acquired by the S. typhimurium lineage and that this element is likely not involved in the integration or excision of island 4305. CONCLUSION: The "clone-and-transfer" approach of evolutionary study identifies genes whose expression patterns indicate the existence of genera-specific regulatory mechanisms that influence the expression of horizontally-transferred DNA sections. The results provide key information that can be used to facilitate the identification of these regulatory mechanisms.

Bacteria↗
PubMed1999

Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials.

This article provides a systematic review of the frequency and severity of adverse gastrointestinal (GI) events among patients using meloxicam, a cyclooxygenase (COX)-2-selective nonsteroidal anti-inflammatory drug (NSAID). A MEDLINE search of English language articles from 1990-1998, a manual search of citations from primary trials and review articles, and a manual search of proceedings from international gastroenterology meetings were conducted. Randomized clinical trials comparing the frequency of GI adverse events for meloxicam versus non-COX-2-selective NSAIDs were selected. Specific data about the frequency of dyspepsia; perforations, ulcers, and bleeds (PUBs); and withdrawal of medication because of adverse GI events was also extracted. From a pool of 62 potentially relevant citations, 12 randomized trials were identified. All trials concerning symptomatic GI adverse events used the World Health Organization's Adverse Reaction Terminology List (WHO-ARTL) to code adverse events. Patients using meloxicam had fewer GI adverse events compared with non-COX-2-selective NSAIDs (odds ratio = 0.64; 95% confidence interval [CI], 0.59-0.69). Patients using meloxicam experienced less dyspepsia (odds ratio = 0.73; 95% CI, 0.64-0.84), fewer PUBs (odds ratio = 0.52; 95% CI, 0.28-0.96), and less frequent discontinuation of NSAID because of adverse GI events (odds ratio = 0.59; 95% CI, 0.52-0.67) compared with non-COX-2 selective NSAIDs. Meloxicam, a COX-2-selective NSAID, appears to cause fewer adverse GI events than standard, non-COX-2-selective NSAIDs. However, the generalizability of these data may be limited by the low dose of meloxicam used in most trials and the use of the WHO-ARTL to code adverse events.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Natural cognitive coping strategies in schizophrenia.

Recent attention has focused on cognitive-behavioural treatment (CBT) for psychotic thinking. These interventions may be especially appropriate for drug-resistant patients or as an adjunct to pharmacotherapy. However, CBT for schizophrenia was developed in the absence of any systematic investigation of personal self-statements that psychotic individuals develop on their own. The current investigation explored the natural cognitive strategies of 10 community-based persons with schizophrenia. An exploratory interview was employed as the method of inquiry. A data bank of 344 statements was obtained from which 55 pertained to coping strategies. The results were interpreted using the grounded theory method (GTM) of qualitative analysis. Systematic analysis of the meaning units yielded a major category called coping self-talk which pertained to cognitive strategies (the focus of this research report). This category was composed of nine lower-level categories; that is, nine types of self-talk that persons with schizophrenia use actively in their own efforts toward managing psychotic symptoms were identified. These naturalistic coping strategies could provide useful guides for directing cognitive interventions.

Adaptation, Psychological↗
PubMed2005

Systematic mutation analysis of KIAA0767 and KIAA1646 in chromosome 22q-linked periodic catatonia.

BACKGROUND: Periodic catatonia is a familial subtype of schizophrenia characterized by hyperkinetic and akinetic episodes, followed by a catatonic residual syndrome. The phenotype has been evaluated in two independent genome-wide linkage scans with evidence for a major locus on chromosome 15q15, and a second independent locus on chromosome 22qtel. METHODS: In the positional and brain-expressed candidate genes KIAA0767 and KIAA1646, we searched for variants in the complete exons and adjacent splice-junctions as well as in parts of the 5'- and 3'-untranslated regions by means of a systematic mutation screening in individuals from chromosome 22q-linked pedigrees. RESULTS: The mutation scan revealed 24 single nucleotide polymorphisms, among them two rare codon variants (KIAA0767: S159I; KIAA1646: V338G). However, both were neither found segregating with the disease in the respective pedigree nor found at a significant frequency in a case-control association sample. CONCLUSION: Starting from linkage signals at chromosome22qtel in periodic catatonia, we screened two positional brain-expressed candidate genes for genetic variation. Our study excludes genetic variations in the coding and putative promoter regions of KIAA0767 and KIAA1646 as causative factors for periodic catatonia.

Case-Control Studies↗
PubMed2005

Statistical analysis of systematic errors in high-throughput screening.

High-throughput screening (HTS) is an efficient technology for drug discovery. It allows for screening of more than 100,000 compounds a day per screen and requires effective procedures for quality control. The authors have developed a method for evaluating a background surface of an HTS assay; it can be used to correct raw HTS data. This correction is necessary to take into account systematic errors that may affect the procedure of hit selection. The described method allows one to analyze experimental HTS data and determine trends and local fluctuations of the corresponding background surfaces. For an assay with a large number of plates, the deviations of the background surface from a plane are caused by systematic errors. Their influence can be minimized by the subtraction of the systematic background from the raw data. Two experimental HTS assays from the ChemBank database are examined in this article. The systematic error present in these data was estimated and removed from them. It enabled the authors to correct the hit selection procedure for both assays.

Algorithms↗
PubMed2006

Systematic mRNA analysis for the effect of MLH1 and MSH2 missense and silent mutations on aberrant splicing.

A substantial proportion of MLH1 and MSH2 gene mutations in hereditary nonpolyposis colon cancer syndrome (HNPCC) families are characterized by nucleotide substitutions, either within the coding sequence (missense or silent mutations) or in introns. The question of whether these mutations affect the normal function of encoding mismatch DNA repair proteins and thus lead to the predisposition to cancer is determinant in genetic testing. Recent studies have suggested that some nucleotide substitutions can induce aberrant splicing by disrupting cis-transcription elements such as exonic enhancers (ESEs). ESE disruption has been proposed to be the mechanism that underlies the presumed pathological missense mutations identified in HNPCC families. To investigate the prevalence of aberrant splicing resulting from nucleotide substitutions, and its relevance to predicted ESEs, we conducted a systematic RNA screening of a series of 60 patients who carried unrelated exonic or intronic mutations in MLH1 or MSH2 genes. Aberrant splicing was found in 15 cases, five of which were associated with exonic mutations. We evaluated the link between those splicing mutations and predicted putative ESEs by using the computational tools ESEfinder and RESCUE-ESE. Our study shows that the algorithm-based ESE prediction cannot be definitely correlated to experimental observations from RNA screening. By using minigene constructs and in vitro transcription assay, we demonstrated that nucleotide substitutions are the direct cause of the splicing defect. This is the first systematic screening for the effect of missense and silent mutations on splicing in HNPCC patients. The pathogenic splicing mutations identified in this study will contribute to the assessment of "unclassified variants" in genetic counseling. Our results also suggest that one must use caution when determining the pathogenic effect of a missense or silent mutation using ESE prediction algorithms. Analysis at the RNA level is therefore necessary.

Adaptor Proteins, Signal Transducing↗
PubMed2005

LC-MS/MS systematic toxicological analysis: comparison of MS/MS spectra obtained with different instruments and settings.

OBJECTIVES: To compare the mass spectra obtained using a linear-ion-trap (LIT) tandem mass spectrometer (QTRAP) operated in the "enhanced product ion scan" (EPI) mode with those obtained in the classical triple-quadrupole product ion scan (PIS) mode run on the same as well as on two other instruments (TSQ-Quantum and Quattro-Micro). DESIGN AND METHODS: After tentative standardization of ion fragmentation and transmission in both polarities using a reference compound (glafenine) on the three instruments, eight test compounds detected in the positive mode and five in the negative mode were systematically infused in different ionization sources and spectral acquisition performed over approximately 5 s. The relative intensity of the ions present in the resulting spectra was quantitatively and statistically compared. Also, the intra-day and inter-day variabilities of these relative intensities, as well as the effect of increasing compound concentration, were studied using QTRAP operated in EPI mode. RESULTS: The EPI and PIS modes operated on a single LIT MS/MS instrument resulted in significant differences in relative ion intensities in both polarities, and so did the other two instruments despite prior standardization with glafenine. Some fragments could be absent in certain spectra, but no unexpected or unique fragments showed up. Intra-day variability was smaller in the LIT EPI than in the regular PIS mode and in the positive than in the negative polarity. In EPI mode, both intra- and inter-day variabilities increased when the relative intensity decreased. The effect of increasing concentration on the relative intensity of major and minor ions was small but significant in both polarities. Finally, contamination and cleansing of the ionization source also had noticeable effects on MS/MS spectra, though the cause is unclear. CONCLUSIONS: MS/MS spectra do not offer the expected inter-instrument reproducibility despite an attempt at standardizing the fragmentation conditions using a reference compound. However, although the inter-instrument differences in ion relative intensity were significant, the spectra obtained looked almost similar. This suggests that in library searching algorithms, higher weight should be assigned for the m/z ratios than for their relative intensity in the spectra.

Chromatography, Liquid↗
PubMed2006

A systematic genetic analysis in Neisseria meningitidis defines the Pil proteins required for assembly, functionality, stabilization and export of type IV pili.

Although type IV pili (Tfp) are among the commonest virulence factors in bacteria, their biogenesis by complex machineries of 12-15 proteins, and thereby their function remains poorly understood. Interestingly, some of these proteins were reported to merely antagonize the retraction of the fibres powered by PilT, because piliation could be restored in their absence by a mutation in the pilT gene. The recent identification of the 15 Pil proteins dedicated to Tfp biogenesis in Neisseria meningitidis offered us the unprecedented possibility to define their exact contribution in this process. We therefore systematically introduced a pilT mutation into the corresponding non-piliated mutants and characterized them for the rescue of Tfp and Tfp-mediated virulence phenotypes. We found that in addition to the pilin, the main constituent of Tfp, only six Pil proteins were required for the actual assembly of the fibres, because apparently normal fibres were restored in the remaining mutants. Restored fibres were surface-exposed, except in the pilQ/T mutant in which they were trapped in the periplasm, suggesting that the PilQ secretin was the sole Pil component necessary for their emergence on the surface. Importantly, although in most mutants the restored Tfp were not functional, the pilG/T and pilH/T mutants could form bacterial aggregates and adhere to human cells efficiently, suggesting that Tfp stabilization and functional maturation are two discrete steps. These findings have numerous implications for understanding Tfp biogenesis/function and provide a useful groundwork for the characterization of the precise function of each Pil protein in this process.

Bacterial Proteins↗
PubMed2005

Comparing professions through actor-centred governance: community nursing in Britain and Germany.

Professions are increasingly studied from an international perspective, and understanding context is key to cross-national comparison of professions. This paper builds on studies of health service work in different countries and introduces actor-centred governance as a framework for comparing professions. The framework conceptualises context as institutions and, as such, offers a more systematic analysis of context and the interplay between context and actors. The framework is applied to a comparative study of community nursing in Britain and Germany, which includes a local case study of the governance of internal boundaries. Actor-centred governance helps to map out different actors and the interplay among them, to identify different types of institutions, and to trace how institutions relate to actors and vice versa. As such, actor-centred governance allows for a more systematic analysis of similarities and differences, and facilitates comparisons across different countries.

Community Health Nursing↗
PubMed2000

A systematic and quantitative analysis of PCR template contamination.

A quantitative and systematic analysis is provided for ubiquitously present template DNA interfering with the quantification of human DNA by PCR. Two sources contributing to DNA background were identified. The first one is interpreted as DNA present in chemicals and on equipment and the second as caused by operator handling. The amounts were equivalent to 2.5 and 8.9 pg per mL of sample, and the estimated frequencies of contamination were 65 and 35%, respectively, resulting in an effective limit of detection of 17.4 pg/mL. Below this level--named effective laboratory background--a result could not be considered as authentic. Knowledge of these parameters is important for laboratories that analyze minute amounts of human DNA by PCR for purposes such as quantification, typing, and sequencing.

DNA Fingerprinting↗
PubMed2002

Review and meta-analysis of systematic searches for uniparental disomy (UPD) other than UPD 15.

All systematic searches for uniparental disomy (UPD) so far published and comprising clinically defined populations (Silver-Russell syndrome/primordial growth retardation (SRS/PGR) (n = 14), multiple malformations (n = 2), or rare syndromes (n = 12)) or situations at risk (confined placental mosaicism (CPM) (n = 13), spontaneous abortions (n = 6), additional marker chromosomes (n = 15), balanced non-Robertsonian translocations (n = 3), or balanced Robertsonian translocations (n = 15)) were reviewed. In many studies clinical and/or cytogenetic information on fluorescent in situ hybridization (FISH) results was very scarce. Meta-analysis concerning an adequate number of cases was possible for SRS/PGR, CPM, additional marker chromosomes, and balanced Robertsonian translocations only. As expected, the highest risk for UPD was found in cases with translocations between homologous acrocentric chromosomes (11 cases with UPD of 15 investigated) and in CPM due to a meiotic error (25 of 51 cases). In prenatal investigations or in cases with a normal phenotype, translocations between nonhomologous acrocentric chromosomes implied a risk for UPD of less than 0.5%. The risks for maternal UPD 7 in cases with SRS/PGR, for UPD 15 in cases with an additional inv dup(15) marker chromosome, and for UPD of any chromosome in cases with multiple malformation/mental retardation were approximately 5.5%, and approximately 1.3%, respectively. Searches for UPD in well-defined syndromes (Brachmann-De Lange syndrome, Sotos syndrome, Rett syndrome, Weaver syndrome, or XX true hermaphroditism) were disappointing. Not a single case was found.

Abnormalities, Multiple↗
PubMed2003

New molecular methods for classification, diagnosis and therapy prediction of hematological malignancies.

Normal functions of the cell are based on the precise regulation of various genes. If this strict regulation and the hierarchy of genes becomes upset due to flaws in this system, the result will be cellular dysfunction which eventually may lead to carcinogenic transformation. Two basic challenges of the classification of cancers are the discovery of new molecular markers characteristic to defined disease groups and the classification of already diagnosed or new cases into existing groups. This precise classification may open the door to tailored treatment or project the expected outcome of the disease. Today there is unlimited access available to the databases containing sequences and localization of the genes within the confines of Human Genome project. It provides significant help for the discovery of chromosome abnormalities and systematic analysis of gene expression patterns. This is important not only to understand normal functions of the cells, but it also contributes to the identification of new genes that are characteristic to given disease groups as markers and that are potential drug targets. Until the second half of the twentieth century the study of the function and regulation of genes was based on step-by-step investigation of individual genes. Regarding the fact, that the genomes of an increasing number of organisms have become known in whole or in part, numerous new techniques have been developed that facilitated the systematic analysis of gene functions. The aim of this study is to summarize the new, molecular based possibilities for classification, diagnosis and prognosis of hematological malignancies, as well as to summarize the main results of these areas.

Chromosome Aberrations↗
PubMed2003

Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.

A principal challenge currently facing biologists is how to connect the complete DNA sequence of an organism to its development and behaviour. Large-scale targeted-deletions have been successful in defining gene functions in the single-celled yeast Saccharomyces cerevisiae, but comparable analyses have yet to be performed in an animal. Here we describe the use of RNA interference to inhibit the function of approximately 86% of the 19,427 predicted genes of C. elegans. We identified mutant phenotypes for 1,722 genes, about two-thirds of which were not previously associated with a phenotype. We find that genes of similar functions are clustered in distinct, multi-megabase regions of individual chromosomes; genes in these regions tend to share transcriptional profiles. Our resulting data set and reusable RNAi library of 16,757 bacterial clones will facilitate systematic analyses of the connections among gene sequence, chromosomal location and gene function in C. elegans.

Animals↗
PubMed2006

The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents.

BACKGROUND: Little is known about the origin of methylenedioxymethamphetamine (MDMA, ecstasy). The most commonly repeated statement in the medical literature is that MDMA was synthesized by the German pharmaceutical company Merck in 1912 in order to develop an appetite suppressor. AIM: To reconstruct the true story of the first known description of MDMA at Merck using the original documents. METHODS: A systematic analysis of the original documents in Merck's historical archive in Darmstadt, Germany, was conducted (years 1900-60). RESULTS: There were no indications for plans to develop an appetite suppressant at Merck between 1900 and 1960. Although MDMA was, in fact, first synthesized at Merck in 1912, it was not tested pharmacologically because it was only an unimportant precursor in a new synthesis for haemostatic substances. The new pathway was patented in order to evade an existing patent by a local competitor. MDMA was called "Methylsafrylamin" in 1912. In 1927 and 1959, the pharmacological effects of MDMA were studied at Merck, but not in humans. DISCUSSION: A systematic analysis of the original documents in the company's archive revealed that uncritical copy-paste procedures may have contributed to the famous myth that MDMA was patented as an appetite suppressor in 1912.

Appetite Depressants↗
PubMed2001

Classes of enteric nerve cells in the guinea-pig small intestine.

The guinea-pig small intestine has been very widely used to study the physiology, pharmacology and morphology of the enteric nervous system. It also provides an ideal, simple mammalian preparation for studying how nerve cells are organised into functional circuits underlying simple behaviours. Many different types of nerve cells are present in the enteric nervous system and they show characteristic combinations of morphological features, projections, biophysical properties, neurochemicals, and receptors. To identify the different functional classes is an important prerequisite for systematic analysis of how the enteric nervous system controls normal gut behaviour. Based on combinations of multiple-labelling immunohistochemistry and retrograde tracing, it has been possible to account quantitatively for all of the neurones in the guinea-pig small intestine. This article summarises that account and updates it in the light of recent data. A total of 18 classes of neurones are currently distinguishable, including primary afferent neurones, motor neurones, interneurones, secretomotor and vasomotor neurones. It is now possible to take an individual nerve cell and use a few carefully chosen criteria to assign it to a functional class. This provides a firm anatomical foundation for the systematic analysis of how the enteric nervous system normally functions and how it goes wrong in various clinically important disorders.

Animals↗
PubMed2006

Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings.

OBJECTIVE: To perform systematic analysis of current proton magnetic resonance spectroscopy ((1)H MRS) findings in bipolar disorder (BD). METHOD: We grouped the (1)H MRS studies documenting data on the metabolites of N-acetylaspartate (NAA), Choline (Cho), myo-inositol (mI), Glutamate (Glu)/Glutamine (Gln) and Creatine (Cr) separately, for each of the euthymic, manic, depressed adult and child/adolescent bipolar patients. RESULTS: For NAA resonance, 22 studies involving 328 adult bipolar and 349 control subjects were identified. NAA levels were lower in euthymic bipolar patients in the frontal lobe structures and hippocampus. Lithium seems to have an increasing effect on NAA in those brain regions. Available data in children indicates lower NAA levels in euthymic bipolar patients in dorsolateral prefrontal cortex (DLPFC) and cerebellar vermis. Existing data over 25 studies on 366 adult bipolar and 393 control subjects, although inconsistent, may suggest higher Cho/Cr ratios in the basal ganglia (BG) of euthymic bipolar patients. The metabolite mI seems to be increased both in euthymic and manic bipolar children, while most of the available data does not support such alteration in adults. Glu/Gln levels in adult bipolar patients were higher in all mood states compared to controls. Limited data in children supports such an alteration only in the euthymic state. CONCLUSION: The studies reviewed in this paper suggest regional abnormalities of NAA, Cho and Glu/Gln in BD, with the DLPFC, prefrontal and anterior cingulate cortices, hippocampus, and BG being specifically implicated. Systematic analysis of (1)H MRS findings so far helps to define future strategies in this field for delineation of actual neurochemical framework in BD.

Adult↗
PubMed1996

Systematic mutational analysis of the receptor-binding region of the human urokinase-type plasminogen activator.

The amino-terminal fragment of human uPA (ATF; amino acids 1-135), which contains the binding site for the uPA receptor (uPAR, CD87) was expressed in the yeast Saccharomyces cerevisiae. Recombinant yeast ATF, modified and extended by an amino-terminal in-frame insertion of a His6 tract, was purified from total protein extracts by nickel chelate affinity chromatography and shown to be functionally active since it efficiently competes with uPA for binding to cell-surface-associated uPAR. The ATF expression plasmid served as a template for the construction of a series of site-directed mutants in order to define those amino acids that are important for binding to uPAR. All mutant ATF proteins but one (deletion of Ser26) were expressed in a stable form (about 20-30 ng/mg total protein) and the binding capacity of each mutant was tested by a uPA-ligand binding assay employing recombinant uPAR immobilized to a microtiter plate. Each of the 11 amino acids of loop B of the binding region of uPA (amino acids 20-30) were individually substituted with alanine. Lys23, Tyr24, Phe25, IIe28, and Trp30 were important determinants for uPAR binding. A systematic alanine scan was also performed with chemically synthesized linear peptides spanning amino acids 14-32 of ATF. Comparable results to those with the yeast ATF mutants were obtained. In a different set of experiments, those amino acids of the uPAR-binding region of uPA that are only conserved between man and baboon but not in other species were altered: whereas substitution of Thr18 by alanine or Asn32 by serine had hardly any effect, replacement of Asn22 by tyrosine and Trp30 by arginine (both positions are strictly conserved in other mammals) led to ATF variants incapable of interacting with human uPAR. Deletion of either Val20, Ser21, Lys23, His29 or Val20 plus Ser21, respectively, also generated non-reactive ATF mutants. Finally, Lys23 in ATF was substituted with certain amino acids: whereas the replacement of Lys23 by alanine, histidine or glutamine generated ATF variants with moderate uPAR-binding activity, the introduction of a negatively charged amino acid (exchange of Lys23 by glutamic acid) completely abolished uPAR-binding activity. The results presented for the ATF mutants and uPA-derived peptides may provide clues necessary to establish the nature of the physical interaction of uPA with its receptor and may help to develop uPA-derived peptide analogues as potential therapeutic agents to block tumor cell-associated uPA/uPAR interaction.

Amino Acid Sequence↗