Textpresso Central: a customizable platform for searching, text mining, viewing, and curating biomedical literature.

BACKGROUND: The biomedical literature continues to grow at a rapid pace, making the challenge of knowledge retrieval and extraction ever greater. Tools that provide a means to search and mine the full text of literature thus represent an important way by which the efficiency of these processes can be improved. RESULTS: We describe the next generation of the Textpresso information retrieval system, Textpresso Central (TPC). TPC builds on the strengths of the original system by expanding the full text corpus to include the PubMed Central Open Access Subset (PMC OA), as well as the WormBase C. elegans bibliography. In addition, TPC allows users to create a customized corpus by uploading and processing documents of their choosing. TPC is UIMA compliant, to facilitate compatibility with external processing modules, and takes advantage of Lucene indexing and search technology for efficient handling of millions of full text documents. Like Textpresso, TPC searches can be performed using keywords and/or categories (semantically related groups of terms), but to provide better context for interpreting and validating queries, search results may now be viewed as highlighted passages in the context of full text. To facilitate biocuration efforts, TPC also allows users to select text spans from the full text and annotate them, create customized curation forms for any data type, and send resulting annotations to external curation databases. As an example of such a curation form, we describe integration of TPC with the Noctua curation tool developed by the Gene Ontology (GO) Consortium. CONCLUSION: Textpresso Central is an online literature search and curation platform that enables biocurators and biomedical researchers to search and mine the full text of literature by integrating keyword and category searches with viewing search results in the context of the full text. It also allows users to create customized curation interfaces, use those interfaces to make annotations linked to supporting evidence statements, and then send those annotations to any database in the world. Textpresso Central URL: http://www.textpresso.org/tpc.

Epitopes recognized by human T cells map within the conserved part of the GP190 of P. falciparum.

In a study aimed at developing a vaccine against the asexual blood stages of Plasmodium falciparum, two T cell epitopes were identified within a nonpolymorphic region of gp190 of Plasmodium falciparum merozoites. The two epitopes, which were revealed by deletion analysis, stimulated human T cell clones. Peptides containing sequences of the epitopes stimulated the cloned T cells and peripheral blood mononuclear cells (PBMC) from malaria-infected individuals. Moreover, the T cell clones responded to 11 different Plasmodium falciparum isolates in culture, showing that the epitopes are recognized in native parasites.

Substitution of the thioredoxin system for glutathione reductase in Drosophila melanogaster.

The disulfide reducing enzymes glutathione reductase and thioredoxin reductase are highly conserved among bacteria, fungi, worms, and mammals. These proteins maintain intracellular redox homeostasis to protect the organism from oxidative damage. Here we demonstrate the absence of glutathione reductase in Drosophila melanogaster, identify a new type of thioredoxin reductase, and provide evidence that a thioredoxin system supports GSSG reduction. Our data suggest that antioxidant defense in Drosophila, and probably in related insects, differs fundamentally from that in other organisms.

Innate immune defense against malaria infection in the mosquito.

Anopheles gambiae, the most important vector of malaria, employs its innate immune system in the fight against Plasmodium. This can affect the propagative capacity of Plasmodium in the vector and, in some cases, leads to total refractoriness to the parasite. The components operating in the mosquito's innate immune system and their potential relevance to antimalarial responses are being systematically dissected.

Natural occurrence of Fusarium toxins in soy food marketed in Germany.

A total of 45 samples of soy food including whole beans, roasted soy nuts, flour and flakes, textured soy protein, tofu, proteinisolate including infant formulas and fermented products (soy sauce) were randomly collected in food and health food stores and analysed for Fusarium toxins. A spectrum of 13 trichothecenes of the A-type as well as of the B-type were determined by gas chromatography/mass spectrometry, zearalenone (ZEA), alpha- and beta-zearalenol (alpha- and beta-ZOL) by high performance liquid chromatography (HPLC) with fluorescence and UV-detection. Detection limits ranged between 1 and 19 microg/kg. At least one of the toxins investigated was detected in 11 out of a total of 45 samples of soy food belonging to different commodities. Scirpentriol (SCIRP), 15-monoacetoxyscirpenol, 4,15-diacetoxyscirpenol, T-2 tetraol, HT-2 toxin, deoxynivalenol (DON), 15- and 3-acetyldeoxynivalenol, ZEA, alpha- and beta-ZOL were detected in at least one sample, T-2 triol, T-2, NEO, NIV and FUS-X were not detected in any sample. Five out of 11 samples were positive for one toxin, one sample for two, three, six or seven toxins, two samples for 5 toxins, demonstrating the possibility of a contamination of soy food with a spectrum of Fusarium toxins. SCIRP, DON and ZEA were found up to 108, 260 and 214 microg/kg, the other toxins did not exceed 61 microg/kg. A first insight into the contamination of soy food with a broad spectrum of Fusarium toxins is provided.

Methylation and silencing of the retinoic acid receptor-beta2 gene in breast cancer.

BACKGROUND: A growing body of evidence supports the hypotheses that the retinoic acid receptor beta2 (RAR-beta2) gene is a tumor suppressor gene and that the chemopreventive effects of retinoids are due to induction of RAR-beta2. RAR-beta2 expression is reduced in many malignant tumors, and we examined whether methylation of RAR-beta2 could be responsible for this silencing. METHODS: RAR-beta2 expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) analysis in eight breast cancer cell lines that were either treated with the demethylating agent 5-aza-2'-deoxycytidine and subsequently with all-trans-retinoic acid (ATRA) or left untreated. Sodium bisulfite genomic sequencing was used to determine the locations of 5-methylcytosines in the RAR-beta2 genes of three of these cell lines. In 16 breast cancer biopsy specimens and non-neoplastic breast tissue, methylation-specific PCR was used to determine the methylation status of RAR-beta2, and, in 13 of the specimens, RT-PCR analysis was used to detect RAR-beta2 expression. RESULTS: Cell lines SK-BR-3, T-47D, ZR-75-1, and MCF7 exhibited expression of RAR-beta2 only after demethylation and treatment with ATRA. The first exon expressed in the RAR-beta2 transcript was methylated in cell lines ZR-75-1 and SK-BR-3. Six breast cancer specimens showed methylation in the same region of the gene. No expression of RAR-beta2 was found in any grade III lesion. An inverse association between methylation and gene expression was found in all grade II lesions. The RAR-beta2 gene from non-neoplastic breast tissue was unmethylated and expressed. CONCLUSIONS: Methylation of the RAR-beta2 gene may be an initial step in breast carcinogenesis; treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality.

Survey of Fusarium toxins in foodstuffs of plant origin marketed in Germany.

A total of 219 samples of foodstuffs of plant origin, consisting of grain-based food, pseudocereals and gluten-free food as well as vegetables, fruits, oilseeds and nuts, were randomly collected during 2000 and 2001 in food and health food stores. A spectra of 13 trichothecene toxins including diacetoxyscirpenol (DAS), 15-monoacetoxyscirpenol (MAS), scirpentriol (SCIRP), T-2 and HT-2 toxins (T-2, HT-2), T-2 triol, T-2 tetraol, neosolaniol (NEO) of the A-type as well as deoxynivalenol (DON), 3- and 15-acetyl-DON (3-, 15-ADON), nivalenol (NIV), and fusarenon-X (FUS-X) of the B-type were determined by gas chromatography/mass spectrometry. Analysis of zearalenone (ZEA), alpha- and beta-zearalenol (alpha- and beta-ZOL) was made by high-performance liquid chromatography with fluorescence and UV-detection. Detection limits ranged between 1 and 19 microg/kg. Out of 84 samples of cereal-based including gluten-free foods, 60 samples were positive for at least one of the toxins DON, 15-ADON, 3-ADON, NIV, T-2, HT-2, T-2 tetraol and ZEA, with incidences at 57%, 13%, 1%, 10%, 12%, 37%, 4% and 38%, respectively, whereas SCIRP and its derivatives MAS and DAS, T-2 triol, Fus-X as well as alpha- and beta-ZOL were not detected in any sample of this subgroup. Contents of DON ranged between 8 and 389 microg/kg, for all other toxins determined concentrations were below 100 microg/kg. The pseudocereals amaranth, quinoa and buckwheat were free of the toxins investigated. Ten of 85 samples of vegetables and fruits were toxin positive. ZEA and the type A trichothecenes MAS, SCIRP, DAS, HT-2 were detected in 7, 3, 2, 1 and 1 samples, respectively. Out of 35 samples of oilseeds and nuts, 7 samples were toxin positive. HT-2, T-2 and ZEA were detected in 4, 3 and 4 samples, respectively. In vegetables and fruits as well as in oilseeds and nuts, toxin levels were below 50 microg/kg. None of the B-type trichothecenes analysed was found for both subgroups.

Gene methylation data--a new challenge for bioinformaticians?

OBJECTIVES: Changes in the status of DNA methylation, known as epigenetic alterations, are among the most common molecular alterations in human neoplasia. For the first time, we reported on the analysis of fecal DNA from patients with CRC to determine the feasibility, sensitivity and specificity of this approach. We want to present basic information about DNA methylation analysis in the context of bioinformatics, the study design and several statistical experiences with gene methylation data. Additionally we outline chances and new research questions in the field of DNA methylation. METHODS: We present current approaches to DNA methylation analysis based on one reference study. Its study design and the statistical analysis is reflected in the context of biomarker development. Finally we outline perspectives and research questions for statisticians and bioinformaticians. RESULTS: Identification of at least three genes as potential DNA methylation-based tumor marker genes (SFRP2, SFRP5, PGR). CONCLUSIONS: DNA methylation analysis is a rising topic in molecular genetics. Gene methylation will push the extension of biobanks to include new types of genetic data. Study design and statistical methods for the detection of methylation biomarkers must be improved. For the purpose of establishing methylation analysis as a new diagnostic/prognostic tool the adaptation of several approaches has become a challenging field of research activity.

Influence of magnesium on blood pressure and the effect of nifedipine in rats.

The influence of long-term alterations in dietary magnesium intake on blood pressure and on the antihypertensive effect of the calcium antagonist nifedipine was investigated in normotensive Wistar-Kyoto (WKY) and in spontaneously hypertensive rats (SHR). The rats were fed a diet either high (1%), normal (0.1%), or low (0.01%) in magnesium for 12 weeks (WKY) and 20 weeks (SHR), respectively. Nifedipine was added to the diet for 4 weeks in concentrations of 300 and 1000 ppm. Each dose was given for 2 weeks. Plasma and intraerythrocytic concentrations of sodium, potassium, and magnesium were measured before and at the end of nifedipine treatment. Blood was obtained by cardiac puncture. In the WKY and SHR, blood pressure was not influenced by magnesium intake. The blood pressure-lowering effect of nifedipine was most pronounced on normal dietary magnesium and was significantly suppressed in the magnesium-deficient rats. Plasma and intracellular total magnesium concentrations were consistently increased during high and reduced during low dietary intake of the ion. Intracellular sodium concentration increased during magnesium deficiency and was normalized by nifedipine. The marked and long-term alterations in plasma and intracellular concentrations of magnesium did not influence arterial blood pressure levels in either the normotensive WKY or the SHR. Therefore, dietary magnesium intake does not appear to play an important role in long-term regulation of blood pressure in rats. However, magnesium depletion attenuates the blood pressure-lowering effect of nifedipine.

Hepatitis C virus, alcoholic cirrhosis, and hepatocellular carcinoma.

We undertook a retrospective study to determine the prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV) infection in 81 Caucasian patients with confirmed hepatocellular carcinoma (HCC). Besides HBV and HCV serological markers, HCV RNA and HBV DNA were detected in serum and liver tissue by polymerase chain reaction. Overall, HCV RNA was found in 20 cases (25%), HBV DNA in 21 patients (26%), and coinfection in 3 patients (3%). HCV RNA in liver tissue was not found without virus in serum, whereas HBV DNA was found in the liver tissue of one patient without viremia. In an additional analysis, 32 patients with HCC and alcoholic cirrhosis (HCC-AC) were compared to 35 cases with AC without HCC and 35 cases with alcoholic hepatitis. The prevalence of HCV RNA in HCC-AC (19%) was significantly higher than in the other groups (AC, 3%; alcoholic hepatitis, 0%). HBV DNA was present in 19% of HCC-AC as compared to 3% of AC and 0% of alcoholic hepatitis. We conclude that the form of HCC in 50% of the patients in a Western European country is related to chronic viral hepatitis. Our data obtained from a group of patients having alcoholic liver disease with or without HCC suggest that the prevalence of HCV RNA or HBV DNA in these populations increases with the severity of hepatic injury.

A new tool for the serodiagnosis of acute Plasmodium falciparum malaria in individuals with primary infection.

We have developed an ELISA which detects, with high specificity, antibodies against a major surface protein of P. falciparum merozoites which is a processing product of the precursor glycoprotein gp190. This assay can be used in the diagnosis of acute malaria in individuals with primary infection. Two partial sequences of gp190 were expressed in E. coli as beta-galactosidase (beta-Gal) fusion proteins. The same sequences fused to chloramphenicol acetyltransferase (CAT) or mouse dihydrofolate reductase (DHFR) react with high frequency when sera of acute malaria patients are analyzed in immunoblots. Antibodies from such sera crosslink, via their antigen binding sites, the beta-Gal fusions to the corresponding CAT or DHFR fusions adsorbed to a solid phase as demonstrated by the captured beta-Gal activity. The assay is highly specific, shows extremely low cut off values and should therefore be widely applicable.

The T cell reactivity against the major merozoite protein of Plasmodium falciparum.

We have undertaken a systematic search for T cell epitopes within the sequence of the major merozoite surface antigen (GP190) of Plasmodium falciparum. Recombinant polypeptides expressed in E. coli were used to evaluate the reactivity of peripheral blood mononuclear cells (PBMC) from both inhabitants of a rural community of West Africa exposed to P. falciparum transmission and from German patients with diagnosis of acute malaria. Although the proliferative response of the PBMC was in most cases very low, several T cell clones could be established. Deletion analysis of each gp190-derived polypeptide allowed the identification of six different T cell epitopes. Epitopes could be mapped within the dimorphic region of gp190, which also contains the sequences most frequently recognized by sera from adult individuals living in endemic areas.

Minor chromosome variants in child psychiatric patients.

The frequency of minor chromosome variants, as detected by conventional chromosome analysis, was examined among 1,289 child psychiatric patients, of whom one-fourth had only behavioral problems and three-fourths had congenital abnormalities and more severe mental disorders. There was no more than random association between prominent satellites, prominent secondary constrictions or a long Y chromosome, and congenital abnormalities or more severe mental disorders. The frequencies of these chromosome variants were affected by race as has been shown in previous studies. These findings do not support the evidence for a developmental effect of minor variants in man.

Noninvasive measurement of pulmonary vascular resistances by assessment of cardiac output and pulmonary transit time.

RATIONALE AND OBJECTIVES: Pulmonary vascular resistance is of special interest in many diseases. Usually it is determined invasively by catheterization, but cardiac output and pulmonary transit time can be ascertained by several noninvasive methods. METHODS: Fourteen heart recipients (age 34-71 years) were examined by electron-beam CT of the heart. Cine and flow studies were performed using a total of 60 mL of contrast and a breath-hold of 20 seconds. RESULTS: A mathematical model for calculating pulmonary vascular resistances from noninvasively measured cardiac outputs and pulmonary transit times was developed. Right-sided heart catheterization served as the reference method. CONCLUSIONS: The formula created seems to allow a clinically valid estimate of pulmonary vascular resistance from noninvasively acquired data.

Event-related potentials elicited by spoken relative clauses.

Sentence-length event-related potential (ERP) waveforms were obtained from 23 scalp sites as 24 subjects listened to normally spoken sentences of various syntactic structures. The critical materials consisted of 36 sentences each containing one of two types of relative clauses that differ in processing difficulty, namely Subject Object (SO) and Subject Subject (SS) relative clauses. Sentence-length ERPs showed several differences in the slow scalp potentials elicited by SO and SS sentences that were similar in their temporal dynamics to those elicited by the same stimuli in a word-by-word reading experiment, although the effects in the two modalities have non-identical distributions. Just as for written sentences, there was a large, fronto-central negativity beginning at the linguistically defined "gap" in the SO sentences; this effect was largest for listeners with above-median comprehension rates and is hypothesized to index changes in on-line processing demands during comprehension.

Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrP(C).

In interspecies transmissions of transmissible spongiform encephalopathies, the agent has to overcome a species barrier that is largely influenced by the rate of homology between the prion proteins (PrP(C)) of the two involved species. Generating transgenic mice expressing PrP(C) of a foreign species is an approach to develop TSE models that are at least partly devoid of a species barrier. The availability of such animals would enable the detection of low doses of infectivity in tissues or bodily fluids derived from other species. We generated transgenic mice that overexpress bovine PrP(C) (Tgbov XV mice) for the development of an improved detection assay for cattle derived BSE prions. These mice succumbed to the disease 250 days after inoculation with a brain homogenate from BSE diseased cattle. Diagnosis of BSE in transgenic mice was confirmed using Western blot, as well as histological and immunohistochemical methods. In contrast, transgenic mice overexpressing murine PrP(C) (tga20 mice) did not display shorter incubation times than nontransgenic RIII mice infected with the same inoculum. The expression of a chimaeric PrP of murine and bovine sequences rendered such mice partly, if not entirely resistant to an infection with the BSE agent.

B-lymphocytes are predominantly involved in viral propagation of hepatitis C virus (HCV).

Recent reports have shown that HCV infection is not only restricted to hepatocytes. Like hepatitis B virus (HBV), which also was thought to be strictly hepatotropic in early molecular and cellular investigations, infection of lymphoid cells by HCV in vivo has been demonstrated. We showed that total peripheral blood leukocytes of chronically HCV-infected patients are infected by detection of plus- and minus-stranded HCV RNA using strand-specific oligonucleotide primers in the RT-PCR. These cells also represent extrahepatic sites for the viral replication, as demonstrated by incorporation of [3H]-uridine into nascent RNA after stimulation of the cells with a mitogen. Furthermore, total PBML from an uninfected person could be infected in vitro using an HCV-positive serum. It could be shown that replication of HCV RNA takes place in these cells. Examination of different subsets of PBML showed predominant infection of B-lymphocytes during HCV disease. Additionally, infection of T-lymphocytes was detected in about 50% of all chronically HCV-infected patients.

What's in a name? Electrophysiological differences between spoken nouns, proper names and one's own name.

To investigate the neural processing of different word categories, we recorded event-related potentials (ERPs) from 32 individuals listening to sentences, beginning either with a proper name (first name), the subject's own name, or a common noun. Names and nouns both elicited ERP waveforms with the same early componentry, but the N1 and P2 components were larger for proper names than common nouns. The ERPs to the subject's own name also had a large N1/P2 plus a prominent negativity at parieto-central site peaking around 400 ms and a late positivity between 500-800 ms over left lateral-frontal sites. These findings are consistent with differential processing of people's first names within the category of nouns.

Theta synchronization predicts efficient memory encoding of concrete and abstract nouns.

Functional and topographical differences between processing of spoken nouns which were remembered or which were forgotten were shown by means of EEG coherence analysis. Later recalled nouns were related with increased neuronal synchronization (= cooperation) between anterior and posterior brain regions regardless of presented word category (either concrete or abstract nouns). However, theta coherence exhibited topographical differences during encoding of concrete and abstract nouns whereby former were related with higher short-range (mainly intrahemispheric), later with higher long-range (mainly interhemispheric) coherence. Thus, theta synchronization possibly is a general phenomenon always occurring if task demand increases and more efficient information processing is required. Measurement of EEG coherence yields new information about the neuronal interaction of involved brain regions during memory encoding of different word classes.

A comparison of captopril and digoxin in the treatment of patients with mild-to-moderate chronic congestive heart failure.

In a double-blind study, 116 patients (mean age, 57.6 years) with mild-to-moderate chronic congestive heart failure who were in sinus rhythm were randomly assigned to receive 25 mg of captopril twice daily (up to 50 mg twice daily, if needed) plus hydrochlorothiazide (HCTZ) (group 1) or 0.1 mg of digoxin twice daily plus HCTZ (group 2) for 12 months. During a 3- to 4-week pretreatment stabilization period, group 1 received a mean of 37.7 mg of HCTZ daily and group 2 received 34.9 mg daily. After 6 weeks and 12 months of treatment, improvement was noted in both treatment groups on five measures of cardiac function: exercise tolerance, left ventricular end-diastolic diameter (LVEDD), ejection fraction, blood pressure, and heart rate. At 12 months, significantly greater improvement was noted in group 1 than in group 2 in exercise tolerance (from 329 seconds at baseline to 445 seconds at 12 months in group 1 and from 353 to 427 seconds in group 2; P < 0.05); LVEDD (from 60.5 to 56.5 mm in group 1 and from 60.3 to 57.9 mm in group 2; P < 0.05); and blood pressure (from 103.5 to 95.6 mm Hg in group 1 and from 101.9 to 97.0 mm Hg in group 2; P < 0.03). Clinical severity (New York Heart Association class) improved in both groups; 52% of the patients in group 1 and 41% in group 2 dropped an average of one functional class (P < 0.01). The results indicate that captopril combined with a diuretic is an effective initial treatment for patients with mild-to-moderate congestive heart failure.