From 5437632e2e8a4d5174ac9d3bf7b33e1ae06a444a Mon Sep 17 00:00:00 2001 From: Olivier Filangi Date: Tue, 22 Oct 2024 08:40:43 +0200 Subject: [PATCH 1/6] add management json_dir --- config/msd_spark.json | 51 +++++++++++++++++++ ...be90-eb7f-4950-8ef0-98d9dbbbcd38-c000.json | 30 +++++++++++ ...be90-eb7f-4950-8ef0-98d9dbbbcd38-c001.json | 30 +++++++++++ ...be90-eb7f-4950-8ef0-98d9dbbbcd38-c002.json | 30 +++++++++++ ...be90-eb7f-4950-8ef0-98d9dbbbcd38-c003.json | 10 ++++ .../abstract/abstract_manager.py | 45 ++++++++++++---- 6 files changed, 186 insertions(+), 10 deletions(-) create mode 100644 config/msd_spark.json create mode 100644 data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c000.json create mode 100644 data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c001.json create mode 100644 data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c002.json create mode 100644 data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c003.json diff --git a/config/msd_spark.json b/config/msd_spark.json new file mode 100644 index 0000000..39b1b2f --- /dev/null +++ b/config/msd_spark.json @@ -0,0 +1,51 @@ +{ + "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", + "threshold_similarity_tag_chunk" : 0.65, + "threshold_similarity_tag" : 0.80, + "batch_size" : 32, + + "populate_owl_tag_embeddings" : { + "ontologies": { + "planteome_link" : { + "peco": { + "url": "http://purl.obolibrary.org/obo/peco.owl", + "prefix": "http://purl.obolibrary.org/obo/PECO_", + "format": "xml", + "label" : "", + "properties": [""] + }, + "po": { + "url": "http://purl.obolibrary.org/obo/po.owl", + "prefix": "http://purl.obolibrary.org/obo/PO_", + "format": "xml", + "label" : "", + "properties": [""] + }, + "pso": { + "url": "http://purl.obolibrary.org/obo/pso.owl", + "prefix": "http://purl.obolibrary.org/obo/PSO_", + "format": "xml", + "label" : "", + "properties": [""] + }, + "to": { + "url": "http://purl.obolibrary.org/obo/to.owl", + "prefix": "http://purl.obolibrary.org/obo/TO_", + "format": "xml", + "label" : "", + "properties": [""] + } + } + }, + "debug_nb_terms_by_ontology" : -1 + }, + "populate_ncbi_taxon_tag_embeddings" : { + "tags_per_file" : 10000 + }, + "populate_abstract_embeddings" : { + "abstracts_per_file" : 500, + "from_file" : { + "json_dir" : "data/abstracts/msd-arch" + } + } +} diff --git a/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c000.json b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c000.json new file mode 100644 index 0000000..94d4466 --- /dev/null +++ b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c000.json @@ -0,0 +1,30 @@ +{"title":"Expression and localization of laminin-5 subunits during mouse tooth development.","abstract":"Tooth morphogenesis is regulated by epithelial-mesenchymal interactions mediated by the basement membrane (BM). Laminins are major glycoprotein components of the BMs, which are involved in several cellular activities. The expression and localization of the alpha3, beta3, and gamma2 laminin-5 subunits have been analyzed by in situ hybridization and immunohistochemistry during mouse molar development. Initially (E12), mRNAs of all subunits were detected in the entire dental epithelium and the corresponding proteins were located in the BM. During cap formation (E13-14), transcripts for the alpha3 and gamma2 subunits were localized in the outer dental epithelium (ODE), whereas the beta3 subunit mRNA was present in the inner dental epithelium (IDE). During the early bell stage (E16), immunoreactivity for all subunits disappeared from the BM along the IDE, although intense signals for beta3 mRNA were detectable in cells of the IDE. Subsequently, when the dentinal matrix was secreted by odontoblasts (E18-19.5), mRNAs of all three subunits were re-expressed by ameloblasts, and the corresponding proteins were detected in ameloblasts and in the enamel matrix. Tissue recombination experiments demonstrated that when E16 IDE or ODE was associated with E18 dental papilla mesenchyme, immunostaining for all laminin-5 subunits disappeared from the BM, whereas when cultured with non-dental limb bud mesenchyme, they remained positive after 48 hr of culture. These results suggest that the temporospatial expression of laminin-5 subunits in tooth development, which appears to be differentially controlled by the dental mesenchyme, might be related to the enamel organ histo-morphogenesis and the ameloblast differentiation.","doi":"10.1002/(SICI)1097-0177(199802)211:2<164::AID-AJA5>3.0.CO;2-F","pmid":"9489770"} +{"title":"Aphakia (ak), a mouse mutation affecting early eye development: fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern.","abstract":"The homozygous mouse mutant aphakia (ak) has been characterized by bilaterally aphakic eyes without a pupil [Varnum DS, Stevens, LC (1968): J Hered 59:147-150]. The mutation was mapped to chromosome 19 [Varnum DS, Stevens, LC (1975): Mouse News Lett 53:35]. Our linkage studies yielded a precise localization of the ak gene 0.6 +/- 0.3 cM proximal to the microsatellite marker D19Mit10 and 0.7 +/- 0.4 cM distal to D19Mit4 and D19Mit91. No recombination was found with the marker D19Mit9 among 418 backcross offspring tested. The developmental control gene Pax2 mapped 11.0 +/- 3.5 cM proximal to ak and is excluded as a candidate gene. Sequence analysis of Fgf8 and Chuk1, which are localized close to the marker D19Mit10, detected no mutations in the ak/ak mutants. Histological analysis of homozygous mutants suggested the arrest of lens development at the lens stalk stage, a transient morphological structure during the formation of the lens vesicle. In the lens remnants, Pax6 and Six3 are expressed, whereas in the persisting lens stalk only Pax6 was detected. The expression pattern of Pax2 appeared normal; Cryaa expression could not be detected. As a consequence of the arrested lens development, other ocular tissues that require for their development information from the intact lens, such as iris, ciliary muscle, retina, and vitreous body, are absent or formed abnormally.","doi":"10.1002/(SICI)1520-6408(1998)23:4<299::AID-DVG5>3.0.CO;2-G","pmid":"9883582"} +{"title":"Inhibition of pea chloroplast DNA helicase unwinding and ATPase activities by DNA-interacting ligands.","abstract":"DNA helicases unwind the duplex DNA in an ATP dependent manner and thus play an essential role in DNA replication, repair, recombination and transcription. Any DNA-interacting ligand which will modulate DNA helicase activity may interrupt practically all kinds of DNA transactions. There are no studies on the effect of various cytotoxic DNA-interacting ligands on organelle helicases. We have determined the effect of camptothecin, VP-16 (etoposide), ellipticine, genistein, novobiocin, m-AMSA, actinomycin C1, ethidium bromide, daunorubicin and nogalamycin on unwinding and ATPase activities of purified chloroplast DNA helicase from pea (Pisum sativum). Our study has shown that DNA-intercalating ligands actinomycin C1, ethidium bromide, daunorubicin and nogalamycin were inhibiting the DNA unwinding activity with an apparent Ki of 2.9 microM, 3.0 microM, 1.4 microM and 1.0 microM, respectively. These four inhibitors also inhibited the ATPase activity of pea chloroplast DNA helicase. These results indicate that the intercalation of the inhibitors into DNA generates a complex that impedes the translocation of chloroplast DNA helicase, resulting in both inhibition of unwinding activity and ATP hydrolysis. This study would be useful for understanding the mechanism of organelle DNA helicase unwinding and the mechanism by which these DNA-interacting ligands inhibit cellular function.","doi":"10.1006/bbrc.1998.8363","pmid":"9535757"} +{"title":"Restoration of a stem-loop structure required for potato virus X RNA accumulation indicates selection for a mismatch and a GNRA tetraloop.","abstract":"The 5' region of potato virus X (PVX) RNA contains a stem-loop structure, stem-loop 1 (SL1), that is required for efficient plus-strand RNA accumulation. To determine how changes to individual elements in SL1 are accommodated by the virus, we inoculated PVX transcripts containing modifications in the terminal tetraloop (TL), stem C (SC), and stem D (SD) regions onto Nicotiana benthamiana plants and analyzed progeny RNAs over a series of passages. Several progeny RNAs isolated from plants inoculated with the TL mutants containing changes to the first nucleotide of the GAAA motif or deletion of the entire TL sequence were found to contain multiple A insertions within the terminal loop region. The wild-type TL motif, GAAA, was recovered for all TL mutants by the second passage, suggesting that the sequence and potential structure of this element are crucial for PVX infection. Revertant RNAs isolated from plants inoculated with mutants in SD and the central region of SC indicated that increased stem length is tolerated. Restoration of SD length to the 4 bp typical of the wild-type PVX RNA was accompanied by A insertion into loop C. Mutants with a conversion of the C55-C78 mismatch to a G-C pair, relocation of this mismatch within the central region of SC, or deletion of C55-C78 were unable to infect protoplasts and plants. In contrast, the mutant with a conversion of the C55-C78 mismatch to an A-C mismatch, which exhibited low levels of PVX plus-strand RNA in protoplasts, was able to infect plants and quickly reverted to the wild-type C-C mismatch. These data indicate that important sequence and secondary structural elements within SL1 are required for efficient viral infection and that multiple A insertions within the TL and loop C regions, potentially by polymerase stuttering, accompany restoration of SL1 structure.","doi":"10.1006/viro.1999.9843","pmid":"10417268"} +{"title":"The first triple gene block protein of peanut clump virus localizes to the plasmodesmata during virus infection.","abstract":"The subcellular localization of the first triple gene block protein (TGBp1) of peanut clump pecluvirus (PCV) was studied by subcellular fractionation and immunogold cytochemistry using TGBp1-specific antibodies raised against a fusion protein expressed in and purified from bacteria. In the inoculated and apical leaves of virus-infected Nicotiana benthamiana, TGBp1 localized to the cell wall and P30 fractions. Electron microscopy of immunogold-decorated ultrathin sections of the infected leaf tissue revealed TGBp1-specific labeling of the plasmodesmata joining mesophyll cells. In longitudinal sections of the plasmodesmata, the TGBp1-specific labeling was most commonly associated with the plasmodesmal collar region. In transgenic N. benthamiana, which constitutively expressed TGBp1, no TGBp1-specific immunogold labeling of plasmodesmata was observed, but plasmodesmata were gold decorated when the transgenic plants were infected with a TGBp1-defective PCV mutant, indicating that factors induced by the virus infection target and/or anchor the transgene TGBp1 to the plasmodesmata.","doi":"10.1006/viro.1999.9997","pmid":"10544148"} +{"title":"A comparative study of Tam3 and Ac transposition in transgenic tobacco and petunia plants.","abstract":"Transposition of the Anthirrinum majus Tam3 element and the Zea mays Ac element has been monitored in petunia and tobacco plants. Plant vectors were constructed with the transposable elements cloned into the leader sequence of a marker gene. Agrobacterium tumefaciens-mediated leaf disc transformation was used to introduce the transposable element constructs into plant cells. In transgenic plants, excision of the transposable element restores gene expression and results in a clearly distinguishable phenotype. Based on restored expression of the hygromycin phosphotransferase II (HPTII) gene, we established that Tam3 excises in 30% of the transformed petunia plants and in 60% of the transformed tobacco plants. Ac excises from the HPTII gene with comparable frequencies (30%) in both plant species. When the beta-glucuronidase (GUS) gene was used to detect transposition of Tam3, a significantly lower excision frequency (13%) was found in both plant species. It could be shown that deletion of parts of the transposable elements Tam3 and Ac, removing either one of the terminal inverted repeats (TIR) or part of the presumptive transposase coding region, abolished the excision from the marker genes. This demonstrates that excision of the transposable element Tam3 in heterologous plant species, as documented for the autonomous element Ac, also depends on both properties. Southern blot hybridization shows the expected excision pattern and the reintegration of Tam3 and Ac elements into the genome of tobacco plants.","doi":"10.1007/BF00016137","pmid":"2562396"} +{"title":"Characterization of a Gy4 glycinin gene from soybean Glycine max cv. forrest.","abstract":"The glycinin gene family encoding the glycinin subunits in soybean plants is composed of at least five gene members. A genomic clone lambda S312 containing the Gy4 gene from a genomic library of cv. Forrest was isolated and partially characterized. The organization of this gene was found to be similar to that of a null allele from cv. Raiden, but different from the Gy4 gene from cv. Dare. The complete nucleotide sequence of this gene has been determined. It is 2599 bp long consisting of four exons and three introns. Comparing the DNA sequences between this gene and the gene from Dare and a null allele from Raiden, the difference found in the coding region was 5'-GCAGTGCAAG-3' (nt 824 to 833) in the former case versus 5'-TGGAGTTGCAATT-3' (nt 1314 to 1326) in the latter case in the exon 2 domain, resulting in three amino acid differences and one amino acid absence. Some other differences were also found in the non-coding region. The coding sequence and 5'-flanking region of the Gy4 gene, when compared with that of other legumin genes as well as group 1 glycinin subunit genes, revealed some interesting features: (1) a transposable element-like sequence was found in the hypervariable region (HVR) of the exon 3 domain, which was lacking in the legumin and the glycinin group 1 genes; (2) in the 5'-flanking region from nt -145 to -1, two high-homology sequences were found: one from nt -141 to nt -132, the other from nt -118 to nt -92 which includes the 'legumin box' and the RY repeat element.","doi":"10.1007/BF00019204","pmid":"1316192"} +{"title":"The tRNA(Tyr) multigene family of Nicotiana rustica: genome organization, sequence analyses and expression in vitro.","abstract":"Tobacco tRNA(Tyr) genes are mainly organized as a dispersed multigene family as shown by hybridization with a tRNA(Tyr)-specific probe to Southern blots of Eco RI-digested DNA. A Nicotiana genomic library was prepared by Eco RI digestion of nuclear DNA, ligation of the fragments into the vector lambda gtWES.lambda B and in vitro packaging. The phage library was screened with a 5'-labelled synthetic oligonucleotide complementary to nucleotides 18 to 37 of cytoplasmic tobacco tRNA(Tyr). Eleven hybridizing Eco RI fragments ranging in size from 1.7 to 7.5 kb were isolated from recombinant lambda phage and subcloned into pUC19 plasmid. Four of the sequenced tRNA(Tyr) genes code for the known tobacco tRNA1(Tyr) (G psi A) and seven code for tRNA2(Tyr) (G psi A). The two tRNA species differ in one nucleotide pair at the basis of the T psi C stem. Only one tRNA(Tyr) gene (pNtY5) contains a point mutation (T54-->A54). Comparison of the intervening sequences reveals that they differ considerably in length and sequence. Maturation of intron-containing pre-tRNAs was studied in HeLa and wheat germ extracts. All pre-tRNAs(Tyr)--with one exception--are processed and spliced in both extracts. The tRNA(Tyr) gene encoded by pNtY5 is transcribed efficiently in HeLa extract but processing of the pre-tRNA is impaired.","doi":"10.1007/BF00027158","pmid":"1463826"} +{"title":"A new middle repetitive sequence of Nicotiana plumbaginifolia genome.","abstract":"A middle repetitive sequence NPR18 was isolated from Nicotiana plumbaginifolia nuclear genome [8]. Sequences homologous to the repeat are dispersed through genomes of several Nicotiana species. Computer-assisted data analysis of NPR18 primary sequence reveals several features attributed to mobile genetic elements: an AT content higher than average for nuclear DNA of genus Nicotiana plants; a number of direct and inverted repeats. Some of the repeats displayed homology to the terminal and subterminal repeats of Ac/Ds-like plant elements.","doi":"10.1007/BF00029020","pmid":"8219078"} +{"title":"Regulated inactivation of homologous gene expression in transgenic Nicotiana sylvestris plants containing a defense-related tobacco chitinase gene.","abstract":"The class I chitinases are vacuolar proteins implicated in the defense of plants against pathogens. Leaves of transgenic Nicotiana sylvestris plants homozygous for a chimeric tobacco (Nicotiana tabacum) chitinase gene with Cauliflower Mosaic Virus (CaMV) 35S RNA expression signals usually accumulate high levels of chitinase relative to comparable leaves of non-transformed plants. Unexpectedly, some transgenic plants accumulated lower levels of chitinase than nontransformed plants. We call this phenomenon silencing. The incidence of silencing depends on the early rearing conditions of the plants. When grown to maturity in a greenhouse, approximately 25% of plants raised as seedlings in closed culture vessels were of the silent type; none of the plants raised from seed in a greenhouse showed this phenotype. Silencing is also developmentally regulated. Plants showed three patterns of chitinase expression: uniformly high levels of expression in different leaves, uniformly low levels of expression in different leaves, and position-dependent silencing in which expression was uniform within individual leaves but varied in different leaves on the same plant. Heritability of the silent phenotype was examined in plants homozygous for the transgene. Some direct descendants exhibited a high-silent-high sequence of activity phenotypes in successive sexual generations, which cannot be explained by simple Mendelian inheritance. Taken together, the results indicate that silencing results from stable but potentially reversible states of gene expression that are not meiotically transmitted. Gene-specific measurements of chitinase and chitinase mRNA showed that silencing results from co-suppression, i.e. the inactivation of both host and transgene expression in trans. The silent state was not correlated with cytosine methylation of the transgene at the five restriction sites investigated.","doi":"10.1007/BF00279359","pmid":"1281514"} +{"title":"Ultrastructural localization of glycinin and beta-conglycinin in Glycine max (soybean) cv. Maple Arrow by the immunogold method.","abstract":"beta-Conglycinin (7 S globulin) and glycinin (11 S globulin) are the major reserve proteins of soybean. They were localized by the protein A immunogold method in thin sections of Glycine max (soybean) cv. Maple Arrow. In cotyledons, both globulins were simultaneously present in all protein bodies. Statistical analysis of marking intensities indicated no correlation between globulin concentration and size of protein bodies. The immunogold method failed to detect either globulin in the embryonic axis and in cotyledons of four-day-old seedlings. Similar observations were made with cotyledons of two soy varieties lacking either the lectin or the Kunitz trypsin inhibitor. In another variety (T-102) lacking the lectin, the 7 S globulin could not be detected.","doi":"10.1007/BF00493479","pmid":"3759504"} +{"title":"Activation of tumor necrosis factor--alpha system in HIV-1 infection: association with markers of immune activation.","abstract":"The relationships between serum levels of soluble tumor necrosis factor receptors (sTNFRs) and other prognostic and immunological parameters in different immunological subgroups of 64 HIV-1 infected patients were studied. In the patient group as a whole, the raised serum levels of sTNFRs were significantly inversely correlated to the numbers of CD4+ and CD8+ lymphocytes and significantly positively correlated with serum levels of neopterin, HIV-1 p24 antigen and the soluble CD8/CD8+ lymphocyte ratio. However, when the patients were classified into three separate immunological subgroups according to the numbers of CD4+ lymphocytes, only serum levels of neopterin were significantly correlated to levels of sTNFRs in all the defined immunological subgroups. These results indicate that HIV-1 infection is associated with a persistent and chronic immune activation in the TNF system manifested by raised serum levels of sTNFRs, which may reflect sustained activation of the immune system particularly in monocytes/macrophages. Further, these results confirm that, when comparing immunological and virological parameters in HIV-1 infection, different results may be obtained in different immunological subgroups of patients.","doi":"10.1007/BF01710050","pmid":"7744500"} +{"title":"Endothelial cell coat modifications in rat thoracic aorta. Effect of ovariectomy and cigarette smoke.","abstract":"The effects of acute cigarette smoking and bilateral ovariectomy on the thickness of rat aortic cell coat (Con A) were investigated. Ovariectomized rats showed a significant increase in the thickness of the cell coat. When cigarette smoking was combined with ovariectomy the thickness of the reaction product was similar to controls. Cigarette smoke without ovariectomy resulted in a decreased thickness, but these changes were not significant.","doi":"10.1007/BF01960635","pmid":"6825783"} +{"title":"Control of carbon partitioning and photosynthesis by the triose phosphate/phosphate translocator in transgenic tobacco plants (Nicotiana tabacum). II. Assessment of control coefficients of the triose phosphate/phosphate translocator.","abstract":"Transgenic tobacco (Nicotiana tabacum L.) plants with decreased and increased transport capacities of the chloroplast triose phosphate/phosphate translocator (TPT) were used to study the control the TPT exerts on the flux of starch and sucrose biosynthesis, as well as CO2 assimilation, respiration and photosynthetic electron transport. For this purpose, tobacco lines with an antisense repression of the endogenous TPT (alphaTPT) and tobacco lines overexpressing a TPT gene from Flaveria trinervia (FtTPT) were used. In ambient CO2, there was no or little effect of altered TPT transport activities on either rates of photosynthetic electron transport and/or CO2 assimilation. However, in elevated CO2 (1500 microl x 1(-1)) and low O2 (2%) the TPT exerted strong control on the rate of CO2 assimilation (control coefficient for the wild type; C(J(A))(TPT) = 0.30) in saturating light. Similarly, the incorporation of 14C into starch in high CO2 was increased in tobacco plants with decreased TPT activity, but was reduced in plants overexpressing the TPT from F. trinervia. Thus, the TPT exerted negative control on the rate of starch biosynthesis with a C(J(Starch))(TPT) = -0.19 in the wild type estimated from a hyperbolic curve fitted to the data points. This was less than the positive control strength on the rate of sucrose biosynthesis (C(J(Suc))(TPT) = 0.35 in the wild type). Theoretically, the positive control exerted on sucrose biosynthesis should be numerically identical to the negative control on starch biosynthesis unless additional metabolic pathways are affected. The rate of dark respiration showed some correlation with the TPT activity in that it increased in FtTPT overexpressors, but decreased in alphaTPT plants with an apparent control coefficient of C(J(Res))(TPT) = 0.24. If the control on sucrose biosynthesis is referred to as \"gain of carbon\" (positive control) and the control on starch biosynthesis as well as dark respiration as a \"loss of carbon\" (negative control) for sucrose biosynthesis and subsequent export, the sum of the control coefficients on dark respiration and starch biosynthesis would be numerically similar to the control coefficient on the rate of sucrose biosynthesis. There was also some control on the rate of photosynthetic electron transport, but only at high light and in elevated CO2 combined with low O2. The control coefficient for the rate of photosynthetic electron transport was C(J(ETR))(TPT) = 0.16 in the wild type. Control coefficients were also calculated for plants with elevated and lowered TPT activity. Furthermore, the extent to which starch degradation/glucose utilisation compensates for the lack of triose phosphate export was assessed. The TPT also exerted control on metabolite contents in air.","doi":"10.1007/PL00008146","pmid":"10750895"} +{"title":"Limitations to tobacco mosaic virus infection of turnip.","abstract":"Turnip vein-clearing virus (TVCV) and tobacco mosaic virus (TMV) represent subgroups of tobamoviruses infecting cruciferous and solanaceous plants, respectively. To identify adaptations that may have been necessary in the evolution of the TVCV subgroup from a TMV-like ancestor, the infection of turnip plants by TMV and by chimeras between TMV and TVCV was explored. TMV accumulated at spatially limited sites on inoculated turnip leaves as determined by leaf skeleton hybridization. A plasmid DNA containing a complete TVCV cDNA, when transcribed in vitro, produced RNA that was infectious to tobacco and turnip plants. TVCV-TMV chimeric genomes with junctions within coding regions were not infectious to tobacco, though the movement protein (MP) chimera was infectious to tobacco with a TMV MP transgene. Reciprocal chimeras with junctions between genes were infectious to tobacco. TVCV with a TMV MP gene infected turnips. The other tested chimeras were not detected in non-inoculated leaves, but were found in the inoculated leaves. Thus, the TMV MP is not responsible for the limitation of TMV spread in turnips.","doi":"10.1007/s007050050558","pmid":"10416377"} +{"title":"Ultrastructural demonstration of the carbohydrate in developing rat enamel using soybean agglutinin-gold complexes.","abstract":"Fine structure and organic-inorganic relationships in early immature enamel, and the localization of N-acetyl-D-galactosamine in its matrix, were studied with a post-embedding demineralization and staining method, and a lectin-gold technique, respectively. Organic structures were observed that had similarities in shape but not in size to the original enamel crystals. Particles of colloidal gold coated with soybean agglutinin were scattered in the enamel region on the demineralized, unstained sections. After staining with uranyl acetate and lead citrate, gold particles were observed in close association with organic filamentous structures. These findings suggest that crystals of immature enamel are organic-inorganic structures, the organic structures of which contain N-acetyl-D-galactosamine.","doi":"10.1016/0003-9969(89)90089-7","pmid":"2688615"} +{"title":"Studies on the effective size of phospholipid headgroups in bilayer vesicles using lectin-glycolipid interaction as a steric probe.","abstract":"An experimental approach is described which provides information about the relative, effective size of phospholipid headgroups in bilayer vesicles. It is based on determination of the binding of lectins (Ricinus communis agglutinin or concanavalin A) to synthetic glycolipids inserted in such vesicles, using a vesicle agglutination assay. It is shown that the ability of a glycolipid containing a shorter (4-member) spacer arm to bind the appropriate lectin is highly sensitive to the headgroup structure of the surrounding phospholipid in mixed glycolipid-phospholipid vesicles. Furthermore, when the phospholipid was phosphatidate a change in protonation or in monovalent counter-ion species (Li+, NH+4, N(CH3)+4 or Na+) significantly influenced lectin binding. The interference with lectin binding described above was reduced when the glycolipid spacer arm was extended from a 4- to a 6-member length. Furthermore, the sensitivity to phospholipid headgroup structure or to changes in the ionic environment was completely eliminated when the glycolipid contained a longer (10- or 12-member) spacer arm between the hydrophobic part and the lectin-binding group. It is concluded that the modulation of lectin binding in the former case is due to steric inhibition determined by the effective (hydrated) size of the various phospholipid headgroups.","doi":"10.1016/0005-2736(84)90110-x","pmid":"6704390"} +{"title":"1H NMR study of the conversion of 13(S)-hydroperoxy linoleic acid by soya bean lipoxygenase I.","abstract":"The conversion of 13(S)-hydroperoxy linoleic acid by lipoxygenase I at 298 K was monitored by 1H NMR and ultraviolet absorption spectroscopy. The rate constant for the conversion of the hydroperoxide, k = 45.8 +/- 7.5 M-1 . s-1, depends on the concentrations of both enzyme and hydroperoxide. This constant is not affected by O2, nor by solvent isotope effects.","doi":"10.1016/0005-2760(78)90137-6","pmid":"102362"} +{"title":"A Brassica S-locus gene promoter targets toxic gene expression and cell death to the pistil and pollen of transgenic Nicotiana.","abstract":"The S-locus glycoprotein gene of Brassica is derived from the genetic locus that controls the self-incompatibility response and the specific recognition between pollen and stigma. The promoter of this gene was used to direct expression of the diphtheria toxin A chain gene and the Escherichia coli beta-glucuronidase gene in transgenic Nicotiana tabacum. Expression of the promoter in cells of the pistil and in pollen suggests that a single gene may direct the self-incompatibility response in the two interacting cell types. Additionally, the fusion genes were expressed gametophytically in the heterologous host species, Nicotiana, rather than sporophytically as expected for Brassica. Thus, although the genes involved in self-incompatibility in Brassica and Nicotiana are not homologous in their coding regions, signals for expression of these genes are apparently conserved between the two genera. Our analysis of toxic gene fusion transformants shows that genetic ablation is useful for probing developmental processes and for studying temporal and spatial patterns of gene expression in plants.","doi":"10.1016/0012-1606(91)90064-a","pmid":"1985017"} +{"title":"Phenotypic changes of human smooth muscle cells during development: late expression of heavy caldesmon and calponin.","abstract":"Expression of the regulatory contractile proteins, heavy caldesmon (h-caldesmon) and calponin was studied in human aortic smooth muscle cells (SMCs) during development and compared with the expression of alpha-SM-actin and smooth muscle-myosin heavy chain (SM-MHCs). For this study, novel monoclonal antibodies specific to SM-MHCs, h-caldesmon, and calponin were developed and characterized. Aortic SMCs from fetuses of 8-10 and 20-22 weeks of gestation express alpha-SM-actin and SM-MHCs, but neither h-caldesmon nor calponin were expressed as demonstrated by immunoblotting and immunofluorescence techniques. In the adult aortic tunica media, SMCs contain all four markers. Thus, the expression of calponin, similar to the expression of alpha-SM-actin, SM-MHCs, and h-caldesmon, is developmentally regulated in aortic SMCs. In the adult aortic subendothelial (preluminal) part of tunica intima, numerous cells containing SM-MHCs, but lacking h-caldesmon and calponin, were found. These results illustrate the similarity of SMCs from intimal thickenings and immature (fetal) SMCs. Expression of contractile proteins in the developing SMCs is coordinately regulated; however, distinct groups of proteins appear to exist whose expression is regulated differently. Actin and myosin, being major contractile proteins, also play a structural role and appear rather early in development, whereas caldesmon and calponin, being involved in regulation of contraction, can serve as markers of higher SMC differentiation steps. In contrast, h-caldesmon and calponin were already present in visceral SMCs (trachea, esophagus) of the 10-week-old fetus. These results demonstrate that the time course of maturation of visceral SMCs is different from that of vascular SMCs.","doi":"10.1016/0012-1606(92)90104-o","pmid":"1397676"} +{"title":"Shuttling of the autoantigen La between nucleus and cell surface after uv irradiation of human keratinocytes.","abstract":"During the past years we have established that the nuclear autoantigen La shuttles between the nucleus and the cytoplasm in tumor cells after inhibition of transcription or virus infection. We reinvestigated this shuttling using primary human keratinocytes from both healthy donors and patients with xeroderma pigmentosum. Ultraviolet irradiation resulted in both an inhibition of transcription and a translocation of La protein from the nucleus to the cytoplasm. After a prolonged inhibition of transcription La protein relocated into the nucleus and assembled with nuclear storage regions. The uv-induced shuttling included a translocation to the cell surface, where La protein colocalized with epidermal growth factor receptors.","doi":"10.1016/0014-4827(90)90002-r","pmid":"2257875"} +{"title":"Molecular chaperones are present in the thylakoid lumen of pea chloroplasts.","abstract":"A soluble protein fraction was obtained from pea chloroplast thylakoids, which represents highly enriched lumenal components. Using antisera against chaperonin 60 (cpn60), chaperonin 10 (cpn10) and the heat shock cognate protein of 70 kDa (hsc70) we are able to demonstrate, that the thylakoid lumen contains a separate set of molecular chaperones, which is distinct from the stromal one. In contrast to the alpha and beta subunits of cpn60 present in the stroma the lumen contains only one cpn60 isoform of distinct isoelectric point. Furthermore the lumenal cpn10 is of 'normal' size and not like its stromal counterpart of a double-domain tandem architecture. The immunoreactive hsc70 isoforms in the lumen seem also to be different from the stromal ones. Thus, chloroplasts seem to contain the largest number of molecular chaperone isoforms present in one organelle.","doi":"10.1016/0014-5793(95)01534-5","pmid":"8603711"} +{"title":"Barnase toxin: a new chimeric toxin composed of pseudomonas exotoxin A and barnase.","abstract":"We have constructed a chimeric toxin composed of Pseudomonas exotoxin A (PE) and the extracellular ribonuclease of Bacillus amyloliquefaciens, barnase. The chimeric protein, termed PE-Bar, reacted with both anti-PE and anti-barnase antisera and had both ADP ribosylation and ribonuclease activities. The chimeric toxin was cytotoxic to the murine fibroblast cell line L929 and to a murine hybridoma resistant to PE. A mutant form of PE-Bar lacking ADP-ribosylating activity was still cytotoxic to L929 cells. Because treatment of cells prelabeld with [3H]uridine resulted in a decrease in their RNA content, we conclude that this cytotoxic effect was due to the ribonuclease activity of barnase molecules that had been translocated to the cytosol. It is now possible to construct chimeric toxins with two or more enzymatic activities that can be delivered to the cytosol of the target cells.","doi":"10.1016/0092-8674(91)90325-s","pmid":"1900455"} +{"title":"Neurotransmitter basis of the behavioral effects of hallucinogens.","abstract":"Indole and phenethylamine-type hallucinogenic drugs were studied in an FR-40 operant behavioral procedure programmed to quantify \"pausing,\"-a behavioral disruption somewhat specific to hallucinatory drug effects. LSD, DOM, DMT and mescaline showed a potency ratio to produce pausing that is well correlated with the hallucinatory potencies of these agents in man. Furthermore, combinations of the hallucinogens interact with potentiation to cause FR-40 pausing, whereas a variety of non-hallucinogenic psychoactive drugs failed to shift the dose-response patterns of pausing for DOM or LSD. Depletion of brain catecholamines by pretreatment with intraventricular 6-OHDA reduced baseline FR-40 rates and attenuated the disruptive effects of d-amphetamine, but failed to modify the dose-response patterns of indole and phenethylamine hallucinogens. On the other hand, pretreatment with intraventricular 5,7-DHT to deplete brain 5-HT potentiated the pause-producing effects of the hallucinogens, although the disruptive effects of phenobarbital were not altered by this pretreatment. Injection of 5,7-DHT into the medial forebrain bundle at the hypothalamic level slightly potentiated LSD, attenuated DOM, and did not affect the pausing produced by mescaline. Metergoline pretreatment shifted the LSD and DMT dose-response curves for pausing to the right by a factor of 2--3, but shifted the DOM and mescaline dose-response patterns to a much greater extent. Metergoline alone slightly increased FR-40 response rates and decreased pausing from baseline levels. The patterns of imparied FR-40 performance induced by d-amphetamine and phenobarbital were unaltered by pretreatment with metergoline. The indole and phenethylamine classes of hallucinogens appear to disrupt this behavior by an agonistic effect at central 5-HT receptors. However, the two classes of drugs may interact with brain 5-HT systems by somewhat different mechanisms.","doi":"10.1016/0149-7634(82)90035-5","pmid":"6817241"} +{"title":"Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response.","abstract":"There is now some evidence that major depression may be accompanied by an immune response. The latter condition is suggested by elevated secretion of neopterin and interferon-gamma (IFN gamma) and by lower L-tryptophan (L-TRP) plasma levels. This study investigated the plasma levels of neopterin, L-TRP, and the L-TRP/competing amino acids (CAA) ratio in 30 normal control subjects and 47 depressed subjects (16 minor depressed, 13 simple major depressed, and 18 melancholic subjects), and IFN gamma secretion by mitogen-stimulated peripheral blood mononuclear cells in 7 normal control subjects and 13 major depressed subjects. Plasma neopterin levels were significantly higher in depressed subjects than in normal controls; 61% of melancholic patients had increased neopterin levels (> or = 7 nmol/l) with a specificity of 90%. Patients with major depression had significantly lower L-TRP and L-TRP/CAA values compared with normal control subjects. The amino acid values were significantly and negatively correlated with plasma neopterin levels. Major depressed subjects exhibited significantly higher IFN gamma secretion than did normal control subjects. The results further support the hypothesis that major depression is accompanied by an immune response and that the lower L-TRP availability in that illness may be an epiphenomenon of immune activation.","doi":"10.1016/0165-1781(94)90003-5","pmid":"7761549"} +{"title":"A study of tobacco carcinogenesis. XLII. Bioassay in A/J mice of some structural analogues of tobacco-specific nitrosamines.","abstract":"The tumorigenic activities in A/J mouse lung of the tobacco-specific nitrosamines, N'-nitrosonornicotine (NNN), 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and several structural analogues were evaluated. The analogues were N-nitrosopyrrolidine (NPYR), 5'-carboxy-N'-nitrosonornicotine (CNNN), N-nitrosoproline (NPRO) and 1-(3-pyridyl)-2-buten-1-one (PBO). The results were as follows (dose in mumol per mouse/lung tumors per mouse): NNN (100/1.8 +/- 1.4); NPYR (100/3.9 +/- 1.5); CNNN (200/0.3 +/- 0.5); CNNN (100/0.5 +/- 0.6); NPRO (100/0.6 +/- 0.7); NNK (20/7.2 +/- 3.4); PBO (20/0.7 +/- 1.0); saline control (0.0.5 +/- 0.7). Several conclusions were drawn from this assay. NNK and NPYR were more tumorigenic than NNN. CNNN was non-tumorigenic and thus appears to have potential as a monitor for endogenous formation of tobacco-specific nitrosamines. The alpha,beta-unsaturated ketone PBO does not appear to be an ultimate tumorigen of NNK or NNN.","doi":"10.1016/0304-3835(88)90251-0","pmid":"3180033"} +{"title":"Effect of tobacco extract and N'-nitrosonornicotine on the carcinogen metabolising enzymes under different dietary vitamin B status.","abstract":"Studies were carried out to evaluate the changes in the phase I and II enzymes of xenobiotic metabolism, on treatment with tobacco extract (TE) and a tobacco specific carcinogen, N'-nitrosonornicotine (NNN) in Sprague-Dawley rats maintained on vitamin B complex sufficient and deficient semi-synthetic diets. Both TE and NNN significantly increased the hepatic and pulmonary phase I enzymes in the vitamin B sufficient (SB+) and deficient (SB-) animals. However, the percent increase in enzyme activities was drastically higher in the SB- treated group as compared to those in the SB(+)-treated group. On the other hand, TE and NNN significantly depressed the liver and lung glutathione (GSH) level and glutathione S-transferase (GST) activity in the SB- animals, while the opposite effect was observed in the SB(+)-treated animals. Furthermore, both the treatments depleted the hepatic pool of vitamin A, with a concurrent increase in that of vitamin C in SB+ and SB- groups.","doi":"10.1016/0304-3835(90)90258-y","pmid":"2379138"} +{"title":"Seryl-phosphorylation of soybean nodule sucrose synthase (nodulin-100) by a Ca2+-dependent protein kinase.","abstract":"Sucrose synthase (SS; EC 2.4.1.13) was radiolabeled in situ by incubating detached soybean nodules with 32Pi. Phosphoamino acid analysis indicated that SS was phosphorylated on a serine residue(s). In-vitro phosphorylation of purified nodule SS by desalted nodule extracts was Ca2+-dependent. This SS-kinase was partially purified (approximately 2200-fold) from nodules harvested from illuminated plants. The molecular mass of the SS-kinase was about 55,000 on a Superdex 75 size-exclusion column or in a denaturing autophosphorylation gel. With either purified nodule SS or Syntide 2 as substrate, exogenous calmodulin and phosphatidylserine showed little or no effect on the in-vitro activity of this partially purified protein kinase. However, its activity was inhibited by W-7. The purified nodule SS-kinase (or CDPK) phosphorylated nodule PEP carboxylase (PEPC; EC 4.1.1.31) in the presence of Ca2+. In contrast, a partially purified nodule PEPC-kinase preparation was incapable of phosphorylating nodule SS. Unlike nodule PEPC [Zhang et al. (1995) Plant Physiol. 108, 1561-1568], the phosphorylation state of SS is not likely modulated in planta by photosynthate supply from the shoots.","doi":"10.1016/s0014-5793(97)00537-1","pmid":"9237614"} +{"title":"Expression of chimeric P450 genes encoding flavonoid-3', 5'-hydroxylase in transgenic tobacco and petunia plants(1).","abstract":"Flavonoid-3',5'-hydroxylase (F3'5'H), a member of the cytochrome P450 family, is the key enzyme in the synthesis of 3', 5'-hydroxylated anthocyanins, which are generally required for blue or purple flowers. A full-length cDNA, TG1, was isolated from prairie gentian by heterologous hybridization with a petunia cDNA, AK14, which encodes F3'5'H. To investigate the in vivo function of TG1 and AK14, they were subcloned into a plant expression vector and expressed under the control of the CaMV35S promoter in transgenic tobacco or petunia, both of which originally lack the enzyme. Transgenic petunia plants had a dramatic change in flower color from pink to magenta with a high content of 3',5'-hydroxylated anthocyanins. In contrast, transgenic tobacco plants had minimal color change with at most 35% 3',5'-hydroxylated anthocyanin content. These results indicate that the products of TG1 and AK14 have F3'5'H activity in planta and that interspecific gene transfer alters anthocyanin pigment synthesis. The difference in apparent F3'5'H activity between tobacco and petunia is discussed.","doi":"10.1016/s0014-5793(99)01425-8","pmid":"10567704"} +{"title":"Cellulosome-like sequences in Archaeoglobus fulgidus: an enigmatic vestige of cohesin and dockerin domains.","abstract":"The distribution of cellulosomal cohesin domains among the sequences currently compiled in various sequence databases was investigated. Two cohesin domains were detected in two consecutive open reading frames (ORFs) of the recently sequenced genome of the archaeon Archaeoglobus fulgidus. Otherwise, no cohesin-like sequence could be detected in organisms other than those of the Eubacteria. One of the A. fulgidus cohesin-containing ORFs also harbored a dockerin domain, but the additional modular portions of both genes are undefined, both with respect to sequence homology and function. It is currently unclear what function(s) the putative cohesin and dockerin-containing proteins play in the life cycle of this organism. In particular, since A. fulgidus contains no known glycosyl hydrolase gene, the presence of a cellulosome can be excluded. The results suggest that cohesin and dockerin signature sequences cannot be used alone for the definitive identification of cellulosomes in genomes.","doi":"10.1016/s0014-5793(99)01634-8","pmid":"10606737"} diff --git a/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c001.json b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c001.json new file mode 100644 index 0000000..ed1428e --- /dev/null +++ b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c001.json @@ -0,0 +1,30 @@ +{"title":"Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes.","abstract":"Although it is widely believed that ATP7B is located at the Golgi apparatus, its main localization is in late endosomes. ATP7B seems to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes.","doi":"10.1016/s0016-5085(00)70178-8","pmid":"10784591"} +{"title":"Affinity-purification of a TMV-specific recombinant full-size antibody from a transgenic tobacco suspension culture.","abstract":"A TMV-specific full-size murine IgG-2b/K antibody (mAb24) was expressed in a Nicotiana tabacum cv. Petite Havana SR1 suspension culture (P9s), which was derived from a stably transformed transgenic plant (P9). The integration of an N-terminal murine leader peptide directed the assembled immunoglobulin for secretion. However, in suspension culture, the full-size recombinant antibody, rAb24, was retained by the plant cell wall and was not present in the culture medium. rAb24 expression reached a basal level of 15 microg per gram wet cell weight, corresponding to 0.3% of the total soluble plant cell protein. The level of rAb24 could be increased three-fold by amino acid supplementation of the culture medium. For purification of the recombinant antibody from batch-cultured tobacco suspension cells, the primary plant cell wall was partially digested by enzymatic treatment. This resulted in a total release of recombinant full-size rAb24 into the extraction buffer. A three-step procedure was used to purify the immunoglobulins, starting with cross-flow filtration (step 1) followed by protein A affinity chromatography (step 2) and gel filtration as a final purification step (step 3). This procedure gave a recovery of more than 80% of the expressed rAb24 from plant cell extracts. SDS-PAGE, IEF and immunoblot analyses demonstrated a high degree of homogeneity for the affinity-purified rAb24. An ELISA procedure demonstrated that the specificity and affinity of the protein A affinity purified antibody was indistinguishable from its murine counterpart, indicating the potential of plant cell suspension cultures as bio-reactors for the production of recombinant antibodies.","doi":"10.1016/s0022-1759(99)00058-7","pmid":"10410966"} +{"title":"Spontaneous and chemically induced point mutations in HPRT cDNA of the metabolically competent human lymphoblastoid cell line, MCL-5.","abstract":"Thioguanine-resistant clones of the human lymphoblastoid cell, MCL-5, which carries two recombinant plasmids expressing xenobiotic metabolizing enzymes, were obtained spontaneously and after treatment with 0.1 microgram/ml benzo[a]pyrene (BaP), 1.0 microgram/ml 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK), and 10 micrograms/ml cigarette smoke condensate (CSC). Treatment with the chemicals reduced the cloning efficiency (CE) of MCL-5 cells from about 30% in untreated cultures to about 10% after treatment with NNK and to about 1% or to less than 1% after treatment with CSC or BaP, respectively. At the same time, the mutant frequencies were increased about sevenfold above those of untreated cultures. Among a total of 138 independent mutant clones that had resulted from 55 separate cultures, 60 point mutations were identified within the hypoxanthine guanine phosphoribosyltransferase (HPRT) reading frame by sequencing full-size reverse transcription polymerase chain reaction (RT-PCR) products from thioguanine-resistant clones. The identified 53 coding errors were distributed among 33 locations and types. Among the 30 types of single basepair substitutions leading to coding errors, 12 had not been described before. In the present set of point mutations, the distribution of base substitution types as well as of mutated sites appeared to be influenced by the treatment with the chemicals. Thus, the ratio of G to T transversions increased from 3 among 19 spontaneous point mutations in the HPRT coding region to 9 among 21 BaP-induced point mutations. The G119T and G208T transversions were found three times each, exclusively after treatment with BaP, while the accumulation of two to eight incidences of the G97T, CG142/3TA, C508T, T583A and G599A mutations was split among different treatments. All eight identified point mutations identified after NNK treatment were at G or T residues on either strand that were followed by additional G or T residues.","doi":"10.1016/s0027-5107(99)00183-9","pmid":"10636005"} +{"title":"Effect of Pseudomonas aeruginosa exotoxin A on CD3-induced human T-cell activation.","abstract":"The effect of Pseudomonas aeruginosa (PA) exotoxin A (P-ExA) on CD3-induced T-cell activation was studied on the level of T-cells (proliferation, synthesis of interleukin (IL)-2, expression of IL-2R complex, ICAM-1,2 and LFA-1 molecules), and on the level of monocytes (expression of ICAM-1,2, LFA-1 molecules, as well as FcRI and CD14 receptors). We found that: (1) P-ExA blocked T-cell proliferation and this effect was totally reversed by intact monocytes, and partially by IL-2 or TPA but not by costimulatory cytokines (IL-1alpha, IL-1beta, TNF-alpha or IL-6); (2) P-ExA transiently, in short-term cultures (48 h), inhibited synthesis of IL-2; (3) prolonged stimulation (96 h) of peripheral blood mononuclear cells (PBMC) or CD4 + T-cells with P-ExA in high or low doses (100 and 10 ng/ml, respectively), enhanced the level of IL-2 in the cultures; (4) P-ExA at low dose, combined with IL-1beta, TNF-alpha or IL-6, up-regulated synthesis of IL-2; and (5) stimulation of T-cells with anti-CD3 monoclonal antibody (mAb) and P-ExA at high dose diminished the expression of the p55 chain but not of the p75 chain of IL-2R complex and slightly affected the expression of CD3 complex, ICAM-1,2 and LFA-1 molecules. Hence, P-ExA can regulate the level of IL-2 in cultures of CD3-induced T-cells either by inhibition of IL-2 consumption (when P-ExA is applied in high dose), or by induction of IL-2 production (a costimulatory effect exerted by P-ExA in low dose in combination with monokines). Action of P-ExA on monocytes resulted in: (1) inhibition of the expression of ICAM-1,2 molecules and their ligand LFA-1 molecule; (2) low expression of FcRI receptor (a ligand for Fc part of CD3 mAb); and (3) inhibition (over 90%) of the expression of CD14 molecule. In conclusion, P-ExA-induced anergy of T-cells depends on: (a) decrease in the affinity of IL-2R complex on activated T-cells; and (b) inhibition of the accessory activities of monocytes.","doi":"10.1016/s0165-2478(97)00169-7","pmid":"9657258"} +{"title":"Absence of CD83-positive mature and activated dendritic cells at cancer nodules from patients with hepatocellular carcinoma: relevance to hepatocarcinogenesis.","abstract":"Mature and activated dendritic cells (CD83-positive DCs) are essential for the recruitment and survival of activated tumor-specific lymphocytes during carcinogenesis. The frequencies of CD83 positive DCs were almost same in peripheral blood from patients with hepatocellular carcinoma (HCC) and cirrhosis of liver (LC). However, the numbers of CD83 positive DCs in liver tissues were significant lower in HCC compared with LC (6.6+/-10.9 vs. 33.3+/-24 DCs/specimen, P<0.05). Most importantly, there were no CD83-positive DCs at cancer nodules in HCC. A role of infiltration of activated DCs in liver during hepatocarcinogenesis is shown.","doi":"10.1016/s0304-3835(99)00312-2","pmid":"10680592"} +{"title":"Rat GluR7 and a carboxy-terminal splice variant, GluR7b, are functional kainate receptor subunits with a low sensitivity to glutamate.","abstract":"Glutamate receptors of the kainate-preferring subtype have recently been shown to mediate synaptic transmission in the hippocampus. The low-affinity kainate receptor subunit GluR7 was found to be nonfunctional in previous studies. We report here that the GluR7 subunit and a novel carboxy-terminal splice variant, GluR7b, are functional glutamate receptors with unique pharmacological properties. In particular, glutamate exhibits a 10-fold lower potency for (non-desensitized) GluR7-mediated currents as compared to other non-NMDA receptor channels. These data will facilitate understanding of the distinct role played by GluR7 receptors in synaptic transmission.","doi":"10.1016/s0896-6273(00)80404-3","pmid":"9390526"} +{"title":"Synthesis of azidophospholipids and labeling of lysophosphatidylcholine acyltransferase from developing soybean cotyledons.","abstract":"A photoreactive substrate analog of lysophosphatidylcholine (LPC), 1-([(4-azidosalicyl)-12-amino)]dodecanoyl-sn-glycerol-3-phospho cholin e (azido-LPC) was synthesized. Fast atom bombardment mass spectrometry was employed to confirm the structures of azido-LPC and its intermediates. Azido-LPC was used to label putative acyl-CoA:LPC acyltransferase from microsomal membranes of developing soybean cotyledons. The synthesized substrate analog acts as a substrate for the target acyltransferases and phospholipases in the dark. When the microsomal membranes were incubated with the acyl acceptor analog and immediately photolyzed, LPC acyltransferase was irreversibly inhibited. Photoinactivation of the enzyme by the photoprobe decreased in the presence of LPC. Microsomal membranes were photolyzed with 125I-labeled azido-LPC and analyzed by SDS-PAGE followed by autoradiography. These revealed that the analog preferentially labeled 54- and 114-kDa polypeptides. Substrate protected the labeling of both the polypeptides. In our earlier report, the same polypeptides were also labeled with photoreactive acyl-CoA analogs, suggesting that these polypeptides could be putative LPC acyltransferase(s). These results demonstrated that the photoreactive phospholipid analog could be a powerful tool to label acyltransferases involved in lipid biosynthesis.","doi":"10.1016/s1388-1981(99)00073-6","pmid":"10395964"} +{"title":"Assessment of apparent ileal digestibility of amino acids and nitrogen in cottonseed and soyabean meals fed to pigs determined using ileal dissection under halothane anaesthesia or following carbon dioxide-stunning.","abstract":"Two experiments were conducted to determine apparent ileal digestibility of amino acids (AIDAA) and nitrogen (AIDN) in cottonseed meal (CSM) and soyabean meal (SBM) fed to growing pigs. In the first experiment, twenty-four male pigs (37.3 (SE 2.7) kg) were individually penned and randomized to either CSM or SBM diets. The diets contained 40% of the protein meal (either CSM or SBM) in a wheat starch-sucrose (1:1, w/w) base containing vitamins and minerals, and Cr2O3 as an indigestible marker. Pigs were acclimated to the experimental diets over a 3 d period and on day 4 through to day 14 were offered 1800 g/d of the diet. Diets were offered in three meals/d from day 4 to day 11 and in eight meals/d from day 12 to day 13. After the eighth hourly-meal on day 14, twelve pigs were anaesthetized with halothane while the remaining twelve pigs were CO2-stunned and processed using commercial slaughter procedures. Ileal digesta were collected from a 1500 mm portion of the terminal ileum of each pig and subsequently analysed for amino acids, N, organic matter and Cr. Results indicated that AIDAA of CSM and SBM were lower when digesta were collected following CO2-stunning than when digesta were obtained under halothane anaesthesia. Consistently, AIDN in CSM (0.51 v. 0.56) and SBM (0.55 v. 0.71) were lower (P < 0.05) in CO2-stunned pigs than in halothane-anaesthetized pigs. Furthermore, when digesta collection was conducted under halothane anaesthesia, AIDN of CSM was lower (P < 0.001) than that of SBM. In the second experiment, six male pigs (45 (SE 2.6) kg) were fitted with T-piece cannulas implanted in the terminal ileum, housed individually in metabolism cages, and randomly allocated to either CSM or SBM diets in a single reversal arrangement. Ileal digesta were collected for AIDAA and AIDN determination. Although statistical comparisons could not be made between the two experiments, the AIDAA and AIDN data obtained via cannulated pigs were similar to those values obtained using the halothane-anaesthesia method. Overall, the CO2-stunning method is not recommended for studies of amino acid or nitrogen ileal digestibilities, but may be useful for the study of other dietary constituents.","doi":"10.1017/s0007114598001093","pmid":"9828760"} +{"title":"Kinetic and calcium-binding properties of three calcium-dependent protein kinase isoenzymes from soybean.","abstract":"Calmodulin-like domain protein kinases (CDPKs) are a family of calcium- but not calmodulin-dependent protein kinases found in a wide variety of plants and in protists. CDPKs are encoded by large multigene families, and to assess whether family members play distinct or redundant roles in vivo, we characterized soybean CDPK isoforms alpha, beta, and gamma, which share 60-80% identity in amino acid sequence. RNA blot analysis showed that the three CDPKs were expressed in most plant tissues examined and in suspension-cultured soybean cells. Recombinant CDPKalpha, -beta, and -gamma phosphorylated peptide substrates containing the four-residue motif R/K-X-X-S/T, but CDPKalpha was the most selective for residues outside of the motif. The CDPKs were inhibited by the general protein kinase inhibitors K252a and staurosporine and by calphostin C, which is an inhibitor of protein kinase C. The calcium-binding properties of each CDPK were distinct. The Kd's for Ca2+ determined by flow dialysis in the absence of substrates were 51, 1.4, and 1.6 micro M for CDPKalpha, -beta, and -gamma, respectively. In the presence of the peptide substrate syntide-2 the Kd of CDPKalpha decreased to 0.6 microM. Also, the sensitivity of this isoenzyme's activity to calcium varied with protein substrate. The concentrations of Ca2+ required for half-maximal activity (K0.5) for each CDPK with syntide-2 as substrate were 0.06, 0.4, and 1 micro M, respectively. These results show that members of the CDPK family differ in biochemical properties and support the hypothesis that each isoform may have a distinct role in calcium signal transduction.","doi":"10.1021/bi980062q","pmid":"9578565"} +{"title":"High levels of soluble IFN gamma receptor alpha chain in the plasma of rheumatoid arthritis patients.","abstract":"Soluble receptors for hormones and cytokines have been described. They can serve as natural blockers of their respective ligands. The natural soluble interferon gamma receptor (sIFN gamma R) has been isolated and characterized only in urine. Chromatography of human (hu) plasma from rheumatoid arthritis (RA) patients and controls on immobilized hu IFN gamma or antibodies against IFN gamma R alpha chain permitted us to isolate the sIFN gamma R. The receptor isolated from one control is a protein with a molecular weight between 60-67 kDa depending on the presence of reducing agents. We detected a significantly higher level of plasma sIFN gamma R in patients with rheumatoid arthritis than in apparently healthy subjects.","doi":"10.1023/a:1008087100315","pmid":"9617465"} +{"title":"Promoter/leader deletion analysis and plant expression vectors with the figwort mosaic virus (FMV) full length transcript (FLt) promoter containing single or double enhancer domains.","abstract":"The boundaries required for maximal expression from the promoter/leader region of the full length transcript of figwort mosaic virus (FLt promoter) coupled to reporter genes were defined by 5' and 3' deletion analyses. In transient expression assays using protoplasts of Nicotiana edwardsonii, a 314 bp FLt promoter fragment sequence (-249 to +65 from the transcription start site) was sufficient for strong expression activity. Plant expression vectors developed with modified FLt promoters were tested with GUS or CAT as reporter genes in transgenic plants. The FLt promoter is a strong constitutive promoter, with strength comparable to or greater than that of the CaMV 35S promoter. The FLt promoter with its double enhancer domain linked to GUS or CAT reporter genes provides an average 4-fold greater activity than the FLt promoter with a single enhancer domain (-55 to -249 bp upstream fragment) in tests with transgenic plants and in protoplast transient expression assays.","doi":"10.1023/a:1018477705019","pmid":"9090062"} +{"title":"A productive NADP+ binding mode of ferredoxin-NADP + reductase revealed by protein engineering and crystallographic studies.","abstract":"The flavoenzyme ferredoxin-NADP+ reductase (FNR) catalyzes the production of NADPH during photosynthesis. Whereas the structures of FNRs from spinach leaf and a cyanobacterium as well as many of their homologs have been solved, none of these studies has yielded a productive geometry of the flavin-nicotinamide interaction. Here, we show that this failure occurs because nicotinamide binding to wild type FNR involves the energetically unfavorable displacement of the C-terminal Tyr side chain. We used mutants of this residue (Tyr 308) of pea FNR to obtain the structures of productive NADP+ and NADPH complexes. These structures reveal a unique NADP+ binding mode in which the nicotinamide ring is not parallel to the flavin isoalloxazine ring, but lies against it at an angle of approximately 30 degrees, with the C4 atom 3 A from the flavin N5 atom.","doi":"10.1038/12307","pmid":"10467097","reference_id":"32062302"} +{"title":"Clostridium botulinum can grow and form toxin at pH values lower than 4.6.","abstract":"It is generally accepted that in Clostridium botulinum both growth and toxin formation are completely inhibited at pH values below 4.6. This critical pH value has been confirmed by many investigators using food as substrate or culture media. Occasionally growth of C. botulinum and toxin formation at pH values lower than 4.6 have been reported. In these cases the authors ascribed the unexpected outgrowth and toxin formation to local pH differences in inhomogeneous media and growth of C. botulinum before pH equilibration, or to the fact that fungi created microenvironments within or adjacent to the mycelial mat, where the pH was higher than 4.6 as was demonstrated by Odlaug and Pflug. We show here that the general assumption that C. botulinum does not grow below pH 4.6 is incorrect. We have observed that growth and toxin formation by C. botulinum can take place in homogeneous protein rich substrates (containing 3% or more soya or milk protein) at pH values lower than 4.6.","doi":"10.1038/281398a0","pmid":"39257"} +{"title":"Gene gun-mediated DNA vaccination induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs.","abstract":"DNA vaccination has emerged as an attractive approach for tumor immunotherapy. The aim of this study was to evaluate the potency of DNA vaccines in preventing and treating the liver and lung metastases of a human papillomavirus-16 (HPV-16) E7-expressing murine tumor (TC-1). We used the gene gun method to vaccinate C57BL/6 mice intradermally with DNA vaccines containing the HPV-16 E7 gene, the E7 gene linked to the sorting signals of the lysosome-associated membrane protein-1 (Sig/E7/ LAMP-1), or the 'empty' plasmid vector. The in vivo antitumor immunity was analyzed in both tumor prevention and tumor regression experiments. In addition, cytotoxic T lymphocyte (CTL) assays, enzyme-linked immunospot assay and enzyme-linked immunoabsorbent assay were used to assess the E7-specific T cell-mediated and humoral immunity. Mice vaccinated with Sig/E7/LAMP-1 DNA generated the strongest E7-specific CTL activities, the highest numbers of E7-specific CD8+ cell precursors and the highest titers of E7-specific antibodies. While both E7 DNA and Sig/E7/LAMP-1 DNA generated potent antitumor immunity in the liver and lung metastases models, the Sig/E7/LAMP-1 DNA was more potent under stringent conditions. DNA vaccination with E7-expressing plasmids was effective in controlling liver and lung metastases of an E7-expressing murine tumor. Our data suggest that antigen-specific DNA vaccination can potentially be applied to control liver and lung metastases of tumors with defined tumor-specific antigens.","doi":"10.1038/sj.gt.3301067","pmid":"10637448"} +{"title":"Development and properties of fructose 1,6-bisphosphatase in the endosperm of castor-bean seedlings.","abstract":"1. The activity of fructose 1,6-bisphosphatase (EC 3.1.3.11) in the fatty endosperm of castor bean (Ricinus communis) increases 25-fold during germination and then declines. The developmental pattern follows that of catalase, a marker enzyme for gluconeogenesis in this tissue. 2. The enzyme at its peak of development was partially purified, and its properties were studied. It has an optimal activity at neutral pH (7.0-8.0). The apparent Km value for fructose 1,6-bisphosphate is 3.8 X 10(-5) M. The activity is inhibited by AMP allosterically with an apparent Ki value of 2.2 X 10(-4) M. The enzyme hydrolyses fructose 1,6-bisphosphate and not ribulose 1,5-bisphosphate or sedoehptulose 1,7-bisphosphate. 3. Treatment of the partially purified enzyme with acid leads to an 80% decrease in activity. The remaining activity is insensitive to AMP and has optimal activity at pH 6.7 and a high apparent Km value (2.5 X 10(-4) M) for fructose 1.6-bisphosphate. Enzyme extracted from the tissue with water instead of buffer has a similar modification. The effect of acid explains the discrepancies between this report and previous ones on the properties of the enzyme in this tissue. 4. The storage tissues of various fatty seedlings all contain a 'neutral' fructose 1,6-bisphosphatase. The activities of the enzyme from some of the tissues are inhibited by AMP. 5. The properties of the enzyme in fatty seedlings and in green leaves are discussed in comparison with that in animal tissues.","doi":"10.1042/bj1540647","pmid":"182124","reference_id":"5493246"} +{"title":"Differential in vitro DNA binding activity to a promoter element of the gn1 beta-1,3-glucanase gene in hypersensitively reacting tobacco plants.","abstract":"In a hypersensitive reaction to pathogen infection, expression of the beta-1,3-glucanase gn1 gene is induced in cells surrounding the necrotic lesions. The 5'-flanking sequence of gn1 was examined to investigate the molecular basis controlling activation of gene expression during this plant defense response. Studies on transgenic tobacco plants containing gn1 promoter deletions fused to the beta-glucuronidase reporter gene revealed the presence of negative and positive regulatory sequences mediating both the level and the spatial distribution of gn1 expression. Promoter sequences to -138 bp were sufficient to confer increased gene expression around the necrotic lesions produced in response to Pseudomonas syringae pv. syringae inoculation. It is demonstrated by electrophoretic mobility shift assays that nuclear proteins in both healthy and hypersensitively reacting tobacco leaves interact with DNA sequences within the regulatory elements identified. Among the binding sequences characterized, the promoter region extending from -250 to -217 bp contained the DNA motif -GGCGGC- found to be conserved in most if not all promoters of genes encoding pathogenesis-related basic proteins. The activity bound by this promoter sequence was stronger in hypersensitively responding tissues than in healthy untreated tobacco leaves.","doi":"10.1046/j.1365-313x.1995.7020309.x","pmid":"7704049"} +{"title":"High mobility group proteins HMG-1 and HMG-I/Y bind to a positive regulatory region of the pea plastocyanin gene promoter.","abstract":"A 268 bp region (P268) of the pea plastocyanin gene promoter responsible for high-level expression has been shown to interact with the high mobility group proteins HMG-1 and HMG-I/Y isolated from pea shoot chromatin. cDNAs encoding an HMG-1 protein of 154 amino acid residues containing a single HMG-box and a C-terminal acidic tail and an HMG-I/Y-like protein of 197 amino acid residues containing four AT-hooks have been isolated and expressed in Escherichia coli to provide large amounts of full-length proteins. DNase I footprinting identified eight binding sites for HMG-I/Y and six binding sites for HMG-1 in P268. Inhibition of binding by the antibiotic distamycin, which binds in the minor groove of A/T-rich DNA, revealed that HMG-I/Y binding was 400-fold more sensitive than HMG-1 binding. Binding-site selection from a pool of random oligonucleotides indicated that HMG-I/Y binds to oligonucleotides containing stretches of five or more A/T bp and HMG-1 binds preferentially to oligonucleotides enriched in dinucleotides such as TpT and TpG.","doi":"10.1046/j.1365-313x.1997.11040703.x","pmid":"9161031"} +{"title":"Glyoxalase I from Brassica juncea: molecular cloning, regulation and its over-expression confer tolerance in transgenic tobacco under stress.","abstract":"Despite its ubiquitous presence, the role of glyoxalase I has not been well investigated in plants. In order to find out its physiological functions, we have cloned and characterized a cDNA from Brassica juncea encoding glyoxalase I (Gly I) and made transgenic tobacco plants harbouring Gly I in both sense and antisense orientation. The transgenic nature of the plants was confirmed by Southern blotting, and the estimated number of genes inserted ranged from one to six. The transcript and protein levels of glyoxalase I were also monitored in transgenic plants. The expression of glyoxalase I in B. juncea was upregulated in response to salt, water and heavy metal stresses. In response to a high concentration of salt, the transcript level averaged threefold higher in 72 h, and an increase in the protein was also seen by immunoblotting. The transgenic plants over-expressing glyoxalase I showed significant tolerance to methylglyoxal and high salt, as tested in detached leaf disc senescence assay. A comparison of plants expressing high and low levels of glyoxalase I showed that the tolerance to different salt concentrations was correlated with the degree of glyoxalase I expression. Our results suggest an important role of glyoxalase I in conferring tolerance to plants under stress conditions.","doi":"10.1046/j.1365-313x.1999.00390.x","pmid":"10205896"} +{"title":"Functional characteristics of skate connexin35, a member of the gamma subfamily of connexins expressed in the vertebrate retina.","abstract":"Retinal neurons are coupled by electrical synapses that have been studied extensively in situ and in isolated cell pairs. Although many unique gating properties have been identified, the connexin composition of retinal gap junctions is not well defined. We have functionally characterized connexin35 (Cx35), a recently cloned connexin belonging to the gamma subgroup expressed in the skate retina, and compared its biophysical properties with those obtained from electrically coupled retinal cells. Injection of Cx35 RNA into pairs of Xenopus oocytes induced intercellular conductances that were voltage-gated at transjunctional potentials >/= 60 mV, and that were also closed by intracellular acidification. In contrast, Cx35 was unable to functionally interact with rodent connexins from the alpha or beta subfamilies. Voltage-activated hemichannel currents were also observed in single oocytes expressing Cx35, and superfusing these oocytes with medium containing 100 microm quinine resulted in a 1.8-fold increase in the magnitude of the outward currents, but did not change the threshold of voltage activation (membrane potential = +20 mV). Cx35 intercellular channels between paired oocytes were insensitive to quinine treatment. Both hemichannel activity and its modulation by quinine were seen previously in recordings from isolated skate horizontal cells. Voltage-activated currents of Cx46 hemichannels were also enhanced 1. 6-fold following quinine treatment, whereas Cx43-injected oocytes showed no hemichannel activity in the presence, or absence, of quinine. Although the cellular localization of Cx35 is unknown, the functional characteristics of Cx35 in Xenopus oocytes are consistent with the hemichannel and intercellular channel properties of skate horizontal cells.","doi":"10.1046/j.1460-9568.1999.00607.x","pmid":"10336656"} +{"title":"Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.","abstract":"The xeroderma pigmentosum variant (XPV) is a genetic disease involving high levels of solar-induced cancer that has normal excision repair but shows defective DNA replication after UV irradiation because of mutations in the damage-specific polymerase hRAD30. We previously found that the induction of sister chromatid exchanges by UV irradiation was greatly enhanced in transformed XPV cells, indicating the activation of a recombination pathway. We now have identified that XPV cells make use of a homologous recombination pathway involving the hMre11/hRad50/Nbs1 protein complex, but not the Rad51 recombination pathway. The hMre11 complexes form at arrested replication forks, in association with proliferating cell nuclear antigen. In x-ray-damaged cells, in contrast, there is no association between hMre11 and proliferating cell nuclear antigen. This recombination pathway assumes greater importance in transformed XPV cells that lack a functional p53 pathway and can be detected at lower frequencies in excision-defective XPA fibroblasts and normal cells. DNA replication arrest after UV damage, and the associated S phase checkpoint, is therefore a complex process that can recruit a recombination pathway that has a primary role in repair of double-strand breaks from x-rays. The symptoms of elevated solar carcinogenesis in XPV patients therefore may be associated with increased genomic rearrangements that result from double-strand breakage and rejoining in cells of the skin in which p53 is inactivated by UV-induced mutations.","doi":"10.1073/pnas.130182897","pmid":"10859352","reference_id":"2938222"} +{"title":"Antibiotics induce genome-wide hypermethylation in cultured Nicotiana tabacum plants.","abstract":"Plant genomic DNA methylation was analyzed by an improved SssI methyltransferase assay and by genomic sequencing with sodium bisulfite. Kanamycin, hygromycin, and cefotaxime (also called Claforan) are commonly used as selective agents for the production of transgenic plants. These antibiotics caused DNA hypermethylation in tobacco plants grown in vitro, which was both time- and dose-dependent. An exposure of the plantlets to 500 mg/liter cefotaxime for 1 month caused the de novo methylation of 3 x 10(7) CpG sites/haploid genome of 3.5 x 10(9) base pairs. It occurred in high, moderate, and low repetitive DNA and was not reversible upon the removal of the antibiotics. Reversion was only observed in progeny grown in the absence of drugs. Analysis of the promoter regions of two single-copy genes, an auxin-binding protein gene and the class I chitinase gene, showed the hypermethylation to be heterogeneous but biased toward CpGs. The hypermethylation of the class I chitinase and the auxin-binding protein promoters was not a consequence of a drug-induced gene amplification.","doi":"10.1074/jbc.272.3.1534","pmid":"8999825"} +{"title":"Assembly of chimeric connexin-aequorin proteins into functional gap junction channels. Reporting intracellular and plasma membrane calcium environments.","abstract":"Chimeric proteins comprising connexins 26, 32, and 43 and aequorin, a chemiluminescent calcium indicator, were made by fusing the amino terminus of aequorin to the carboxyl terminus of connexins. The retention of function by the chimeric partners was investigated. Connexin 32-aequorin and connexin 43-aequorin retained chemiluminescent activity whereas that of connexin 26-aequorin was negligible. Immunofluorescent staining of COS-7 cells expressing the chimerae showed they were targeted to the plasma membrane. Gap junction intercellular channel formation by the chimerae alone and in combination with wild-type connexins was investigated. Stable HeLa cells expressing connexin 43-aequorin were functional, as demonstrated by Lucifer yellow transfer. Paris of Xenopus oocytes expressing connexin 43-aequorin were electrophysiologically coupled, but those expressing chimeric connexin 26 or 32 showed no detectable levels of coupling. The formation of heteromeric channels constructed of chimeric connexin 32 or connexin 43 and the respective wild-type connexins was inferred from the novel voltage gating properties of the junctional conductance. The results show that the preservation of function by each partner of the chimeric protein is dictated mainly by the nature of the connexin, especially the length of the cytoplasmic carboxyl-terminal domain. The aequorin partner of the connexin 43 chimera reported calcium levels in COS-7 cells in at least two different calcium environments.","doi":"10.1074/jbc.273.3.1719","pmid":"9430718"} +{"title":"Auxin induction of cell cycle regulated activity of tobacco telomerase.","abstract":"Telomerase activity was measured at each phase of the cell cycle in synchronized tobacco (Nicotiana tabacum) BY-2 cells in suspension culture with the use of the telomeric repeat amplification protocol assay. The activity was low or undetectable at most phases of the cell cycle but showed a marked increase at early S phase. The induction of telomerase activity was not affected by the S phase blockers aphidicolin (which inhibits DNA polymerase alpha) or hydroxyurea (which inhibits ribonucleotide reductase), but it was prevented by olomoucine, an inhibitor of Cdc2/Cdk2 kinases that blocks G(1)-S cell cycle transition. These results suggest that the induction of telomerase activity is not directly coupled to DNA replication by conventional DNA polymerases, but rather is triggered by the entry of cells into S phase. Various analogs of the plant hormone auxin, including indole-3-acetic acid, alpha-naphthaleneacetic acid, and 2,4-dichlorophenoxyacetic acid, potentiated the increase in telomerase activity at early S phase; the growth-inactive analog 2,3-dichlorophenoxyacetic acid, however, had no such effect. Potentiation by indole-3-acetic acid of the induction of telomerase activity was dose dependent. Together, these data indicate that telomerase activity in tobacco cells is regulated in a cell cycle-dependent manner, and that the increase in activity at S phase is specifically inducible by auxin.","doi":"10.1074/jbc.274.30.20997","pmid":"10409648"} +{"title":"Double-blind randomized phase I study on the clinical tolerance and biological effects of natural and recombinant interferon-beta.","abstract":"The clinical tolerance of and the effects recombinant human interferon-beta (rHuIFN-beta) obtained from mammalian cells (Chinese hamster ovary cells) exerts on 2',5'-oligoadenyl (2-5A) synthetase activity, human-Mx protein, neopterin, beta 2-microglobulin, interleukin-1 (IL-1) alpha and beta synthesis were compared to those of natural IFN-beta in 12 healthy volunteers. Each subject received a single i.m. injection of 6 x 10(6) IU rHuIFN-beta and natural IFN-beta according to a randomized double-blind cross-over study design. Both were well tolerated and provoked similar changes in clinical indices. Moreover, rHuIFN-beta and natural IFN-beta induced significant and similar increases in 2'-5' adenylates, human Mx protein, and neopterin levels, but neither modulated beta 2-microglobulin, IL-1 alpha or beta synthesis. The sum of these findings indicates that rHuIFN-beta and natural IFN-beta are biologically equivalent. In view of these results, we are of the opinion that these two types of IFN are probably also therapeutically equivalent and, in consequence, that trials to evaluate the response of viral and neoplastic disease patients to rHuIFN-beta are fully justified.","doi":"10.1089/jir.1992.12.329","pmid":"1431312","reference_id":"31895854"} +{"title":"Gustatory function and dietary habits in users and nonusers of smokeless tobacco.","abstract":"Nicotine and smoking may modify gustatory function or preferences and are associated with altered energy balance; however, there is no information on whether smokeless tobacco (ST) has similar effects. Evaluations of gustatory function (threshold sensitivity, perceived intensity of suprathreshold stimuli, preferences) were conducted on 28 chronic ST users and 30 nonusers after both abstaining and using ST. Subjects also maintained 7-d dietary records that included descriptions of the predominant taste qualities of foods. There were few user vs nonuser differences in gustatory measures. Among nonusers, use of ST reduced perceived intensity of salty, sour, and bitter stimuli. Users reported greater alcohol intakes and lower consumption of carbohydrates, sweet foods, fruits, and grains. Chronic use of ST does not appear to have substantial effects on gustatory function but may be associated with decreased carbohydrate intakes, perhaps related to increased alcohol use and possibly because of reduced consumption of sweet-tasting foods.","doi":"10.1093/ajcn/49.3.482","pmid":"2923081"} +{"title":"Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage.","abstract":"We exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.","doi":"10.1093/ajcn/54.6.1113s","pmid":"1962556","reference_id":"16381205"} +{"title":"Cardiovascular and renal benefits of dry bean and soybean intake.","abstract":"Dry beans and soybeans are nutrient-dense, fiber-rich, and are high-quality sources of protein. Protective and therapeutic effects of both dry bean and soybean intake have been documented. Studies show that dry bean intake has the potential to decrease serum cholesterol concentrations, improve many aspects of the diabetic state, and provide metabolic benefits that aid in weight control. Soybeans are a unique source of the isoflavones genistein and diadzein, which have numerous biological functions. Soybeans and soyfoods potentially have multifaceted health-promoting effects, including cholesterol reduction, improved vascular health, preserved bone mineral density, and reduction of menopausal symptoms. Soy appears to have salutary effects on renal function, although these effects are not well understood. Whereas populations consuming high intakes of soy have lower prevalences of certain cancers, definitive experimental data are insufficient to clarify a protective role of soy. The availability of legume products and resources is increasing, incorporating dry beans and soyfoods into the diet can be practical and enjoyable. With the shift toward a more plant-based diet, dry beans and soy will be potent tools in the treatment and prevention of chronic disease.","doi":"10.1093/ajcn/70.3.464s","pmid":"10479219"} +{"title":"Involvement of 14-3-3 proteins in nuclear localization of telomerase.","abstract":"Maintenance of telomeres is implicated in chromosome stabilization and cell immortalization. Telomerase, which catalyzes de novo synthesis of telomeres, is activated in germ cells and most cancers. Telomerase activity is regulated by gene expression for its catalytic subunit, TERT, whereas several lines of evidence have suggested a post-translational regulation of telomerase activity. Here we identify the 14-3-3 signaling proteins as human TERT (hTERT)-binding partners. A dominant-negative 14-3-3 redistributed hTERT, which was normally predominant in the nucleus, into the cytoplasm. Consistent with this observation, hTERT-3A, a mutant that could not bind 14-3-3, was localized into the cytoplasm. Leptomycin B, an inhibitor of CRM1/exportin 1-mediated nuclear export, or disruption of a nuclear export signal (NES)-like motif located just upstream of the 14-3-3 binding site in hTERT impaired the cytoplasmic localization of hTERT. Compared with wild-type hTERT, hTERT-3A increased its association with CRM1. 14-3-3 binding was not required for telomerase activity either in vitro or in cell extracts. These observations suggest that 14-3-3 enhances nuclear localization of TERT by inhibiting the CRM1 binding to the TERT NES-like motif.","doi":"10.1093/emboj/19.11.2652","pmid":"10835362","reference_id":"4997542"} +{"title":"Regulation of plasmodesmal transport by phosphorylation of tobacco mosaic virus cell-to-cell movement protein.","abstract":"Cell-to-cell spread of tobacco mosaic virus (TMV) through plant intercellular connections, the plasmodesmata, is mediated by a specialized viral movement protein (MP). In vivo studies using transgenic tobacco plants showed that MP is phosphorylated at its C-terminus at amino acid residues Ser258, Thr261 and Ser265. When MP phosphorylation was mimicked by negatively charged amino acid substitutions, MP lost its ability to gate plasmodesmata. This effect on MP-plasmodesmata interactions was specific because other activities of MP, such as RNA binding and interaction with pectin methylesterases, were not affected. Furthermore, TMV encoding the MP mutant mimicking phosphorylation was unable to spread from cell to cell in inoculated tobacco plants. The regulatory effect of MP phosphorylation on plasmodesmal permeability was host dependent, occurring in tobacco but not in a more promiscuous Nicotiana benthamiana host. Thus, phosphorylation may represent a regulatory mechanism for controlling the TMV MP-plasmodesmata interactions in a host-dependent fashion.","doi":"10.1093/emboj/19.18.4875","pmid":"10990451"} +{"title":"Efficient octopine Ti plasmid-derived vectors for Agrobacterium-mediated gene transfer to plants.","abstract":"A two-component cloning system to transfer foreign DNA into plants was derived from the octopine Ti plasmid pTiB6S3. pGV2260 is a non-oncogenic Ti plasmid from which the T-region is deleted and substituted by pBR322. pGV831 is a streptomycin-resistant pBR325 derivative that contains a kanamycin resistance marker gene for plant cells and a site for cloning foreign genes between the 25-bp border sequences of the octopine T-region. Conjugative transfer of pGV831 derivatives to Agrobacterium and cointegration by homologous recombination between the pBR322 sequences present on pGV831 and pGV2260, can be obtained in a single step. Strains carrying the resulting cointegrated plasmids transfer and integrate T-DNA into the genome of tobacco protoplasts, and transformed tobacco calli are readily selected as resistant to kanamycin. Intact plants containing the entire DNA region between the T-DNA borders have been regenerated from such clones. In view of these properties we present pGV831 and its derivatives as vectors for efficient integration of foreign genes into plants.","doi":"10.1093/nar/13.13.4777","pmid":"4022773"} diff --git a/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c002.json b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c002.json new file mode 100644 index 0000000..3bef61f --- /dev/null +++ b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c002.json @@ -0,0 +1,30 @@ +{"title":"Price and consumption of tobacco.","abstract":"Progressive increases in cigarette tax rates provide a powerful contribution to policy for reducing cigarette consumption and generate extra government revenue. The policy has been most effective in groups for whom health publicity effects have been least so, but special provision may be necessary to avoid hardship to poor families.","doi":"10.1093/oxfordjournals.bmb.a011521","pmid":"8746302"} +{"title":"Studies on algal cytochromes. III. Amino acid sequence of cytochrome c-553 from a brown alga, Petalonia fascia.","abstract":"The amino acid sequence of a photosynthetic cytochrome c-553 isolated from a brown alga, Petalonia fascia was determined by BrCN fragmentation and a solid phase Edman degradation. The cytochrome contains 85 amino acid residues, giving a molecular weight of 9,803. The complete amino acid sequence is as follows: Val-Asp-Ile-Asn-Asn-Gly-Glu-Ser-Val-Phe-Thr-Ala-Asn-Cys-Ser-Ala-Cys-His-Ala-Gly -Gly-Asn-Asn-Val-Ile-Met-Pro-Glu-Lys-Thr-Leu-Lys-Lys-Asp-Ala-Leu-Glu-Glu-Asn-Gl u-Met-Asn-Asn-Ile-Lys-Ser-Ile-Thr-Tyr-Gln-Val-Thr-Asn-Gly-Lys-Asn-Ala-Met-Pro-A la-Phe-Gly-Gly-Arg-Leu-Ser-Glu-Thr-Asp-Ile-Glu-Asp-Val-Ala-Asn-Phe-Val-Ile-Ser-Gln-Ser-Gln-Lys-Gly-Trp. The highest homology was found between the sequences of cytochromes c-553 of P. fascia and Alaria esculenta, the next between those of P. fascia and Porphyria tenera.","doi":"10.1093/oxfordjournals.jbchem.a133574","pmid":"6273394","reference_id":"4895156"} +{"title":"Profilins purified from higher plants bind to actin from cardiac muscle and to actin from a green alga.","abstract":"Profilins purified from Zea mays transiently enhance the viscosity of polymerizing cardiac actin at ratios (profilin: actin) < 1, but lower the viscosity at higher ratios. Specific binding of actin from the alga Chara corallina to higher plant profilins suggests strict conservation of interaction between both proteins in plants.","doi":"10.1093/oxfordjournals.pcp.a078668","pmid":"7952964"} +{"title":"Erosive arthritis in systemic lupus erythematosus: analysis of a distinct clinical and serological subset.","abstract":"Erosive arthritis (EA) in systemic lupus erythematosus (SLE) can be debilitating and deforming with uncertain factors for risk, although antibodies to the A2 hnRNP core protein, known as anti-RA33, have been associated with EA. Two hundred patients under long-term follow-up for SLE were evaluated for EA and associated clinical and serological abnormalities. In addition, sera were tested in a masked fashion for anti-RA33 antibodies in a total of 60 patients: 10 with EA and 50 age-, sex- and ethnically matched controls. Ten of 200 (5%) patients with SLE, mainly non-white women, had EA. There were trends for increased renal involvement (P = 0.06), Sjögren's syndrome (P = 0.07) and Raynaud's phenomenon (P = 0.03) in patients with EA compared to those without EA. Rheumatoid factor (RF) was increased in patients with EA (P < 0.02), as were antibodies to double-stranded DNA (P < 0.05), Sm (P < 0.01) and La/SS-B (P < 0.001). Anti-RA33 antibodies were present in 70% with EA compared to 28% without EA (P < 0.05). RF correlated with anti-RA33 antibodies in patients with EA, but not with the presence of anti-RA33 alone. Thus, anti-RA33 antibodies may identify those patients with SLE who are at risk for EA, and an association with RF suggests a common immune response or pathological mechanism in autoimmune erosive joint disease.","doi":"10.1093/rheumatology/37.4.421","pmid":"9619894"} +{"title":"Subcellular localization and in vivo identification of the putative movement protein of olive latent virus 2.","abstract":"The gene encoding the 36.5 kDa ('36K') nonstructural protein located on RNA3 of olive latent virus 2 (OLV-2) was cloned, expressed with the Escherichia coli pGEX-2T system and the purified protein used to raise a polyclonal antiserum. Immunoblot analysis of OLV-2-infected Nicotiana benthamiana plants showed that the 36K protein accumulated in the early stages of infection and was associated with a subcellular fraction enriched in cytoplasmic membranes. In infected cells there were tubular structures, some containing virus-like particles, scattered in the cytoplasm or protruding from or penetrating the cell wall at the plasmodesmata. Immunogold labelling localized the 36K protein in the plasmodesmata of OLV-2-infected cells and showed it to be associated with virus-containing tubules. Leaf trichome cells of N. tabacum plants, transformed with a 36K-green fluorescent protein (GFP) fusion construct, revealed localized fluorescence in the cell walls, possibly due to association of the fusion protein with plasmodesmata. When the same 36K-GFP fusion protein was expressed in N. tabacum protoplasts, long tubular fluorescent structures protruded from the protoplast surface, suggesting that the 36K protein is responsible for tubule induction. The conclusion is drawn that this protein is likely to be the OLV-2 movement protein, mediating cell-to-cell virus movement, and that movement is by a tubule-guided mechanism.","doi":"10.1099/0022-1317-80-5-1103","pmid":"10355755"} +{"title":"Posttranscriptional regulation of ferritin during nodule development in soybean.","abstract":"During soybean (Glycine max) nodule development, induced ferritin mRNA concentration remains elevated while the protein concentration decreases 4- to 5-fold (M. Ragland and E.C. Theil [1993] Plant Mol Biol 21: 555-560). Investigation of posttranscriptional regulation of nodule ferritin during development showed that ferritin mRNA was efficiently translated based on polyribosome size in vivo, protein synthesis (0.8% of total protein) in vitro, and protein synthesis in intact nodules. Ferritin, a plastid protein, was processed in both immature and mature nodules. In chimeric mRNA, soybean ferritin mRNA sequences blocked the function of the iron regulatory element (IRE), the cis regulatory element of animal ferritin mRNA; the IRE regulates chimeric animal mRNAs. The absence of translational regulation of ferritin in plants contrasts with ferritin regulation in animals. Thus, ferritin regulation has diverged during evolution, whereas structure of the mature protein has been conserved. Ferritin in mature soybean nodules is apparently regulated after translation, possibly in analogy with such plastid proteins as chlorophyll-binding proteins D1, CP43, LHCI, and LHCII, the small subunit of ribulose-bisphosphate carboxylase, and apoplastocyanin. An autocatalytic mechanism observed in vivo for degradation of plastid protein D1 and in vitro for pea ferritin during iron release could explain the ferritin decreases in mature nodules.","doi":"10.1104/pp.104.1.263","pmid":"8115547"} +{"title":"Endoplasmic reticulum targeting and glycosylation of hybrid proteins in transgenic tobacco.","abstract":"The correct compartmentation of proteins to the endomembrane system, mitochondria, or chloroplasts requires an amino-terminal signal peptide. The major tuber protein of potato, patatin, has a signal peptide in common with many other plant storage proteins. When the putative signal peptide of patatin was fused to the bacterial reporter protein beta-glucuronidase, the fusion proteins were translocated to the endoplasmic reticulum in planta and in vitro. In addition, translocated beta-glucuronidase was modified by glycosylation, and the signal peptide was correctly processed. In the presence of an inhibitor of glycosylation, tunicamycin, the enzymatically active form of beta-glucuronidase was assembled in the endoplasmic reticulum. This is the first report of targeting a cytoplasmic protein to the endoplasmic reticulum of plants using a signal peptide.","doi":"10.1105/tpc.1.3.381","pmid":"2535509"} +{"title":"HMG I-like proteins from leaf and nodule nuclei interact with different AT motifs in soybean nodulin promoters.","abstract":"Three different nuclear factors recognizing short AT-rich DNA sequences were identified in different organs of soybean. One factor (NAT2) was found to be present in mature nodules, another factor (NAT1) was detected in roots and nodules, and a third one (LAT1) was only observed in leaves. All three factors recognized several DNA sequences in the promoter region of the soybean nodulin N23 gene. Footprinting, deletion, and point mutation analyses revealed different binding properties for all three factors and further showed that even single base pair substitutions had a dramatic effect on binding affinity. The LAT1 and NAT1 factors were released from chromatin by extraction with a low-salt buffer and were soluble in 2% trichloroacetic acid, implying a relationship to high-mobility group (HMG) proteins. DNA binding studies further indicated a functional relationship of these factors to the human HMG I protein. Purification of the LAT1 factor from leaf nuclei revealed the presence of two polypeptides with molecular masses of 21 kilodaltons and 23 kilodaltons, respectively, binding the same DNA sequence with equal affinity.","doi":"10.1105/tpc.2.1.85","pmid":"2152106","reference_id":"2081103"} +{"title":"Factors related to the development of sensitization to green coffee and castor bean allergens among coffee workers.","abstract":"Our findings indicate that castor bean is the major cause of occupational sensitization among coffee workers, whereas smoking and atopy act as enhancing factors.","doi":"10.1111/j.1365-2222.1995.tb01112.x","pmid":"8521183"} +{"title":"Identification of glyA as a symbiotically essential gene in Bradyrhizobium japonicum.","abstract":"A Bradyrhizobium japonicum Tn5 mutant (strain 3160) induced numerous, tiny, white nodules which were dispersed over the whole root system of its natural host plant, soybean (Glycine max). These ineffective, nitrogen non-fixing pseudonodules were disturbed at a very early step of bacteroid and nodule development. Subsequent cloning and sequencing of the DNA region mutated in strain 3160 revealed that the Tn5 insertion mapped in a gene that had 60% homology to the Escherichia coli glyA gene coding for serine hydroxymethyltransferase (SHMT; E.C.2.1.2.1.). SHMT catalyses the biosynthesis of glycine from serine and the transfer of a one-carbon unit to tetrahydrofolate. The B. japonicum glyA region was able to fully complement the glycine auxotrophy of an E. coli glyA deletion strain. Although the Tn5 insertion in B. japonicum mutant 3160 disrupted the glyA coding sequence, this strain was only a bradytroph (i.e. a leaky auxotroph). Thus, B. japonicum may have an additional pathway for glycine biosynthesis. Nevertheless, the glyA mutation was responsible for the drastic symbiotic phenotype visible on plants. It may be possible, therefore, that a sufficient supply with glycine and/or a functioning C1-metabolism are indispensable for the establishment of a fully effective, nitrogen-fixing root nodule symbiosis.","doi":"10.1111/j.1365-2958.1991.tb01824.x","pmid":"2014004","reference_id":"7600314"} +{"title":"Transgenic tobacco plants expressing yeast-derived invertase in either the cytosol, vacuole or apoplast: a powerful tool for studying sucrose metabolism and sink/source interactions.","abstract":"In higher plants sucrose plays a central roles with respect to both short-term storage and distribution of photoassimilates formed in the leaf. Sucrose is synthesized in the cytosol, transiently stored in the vacuole and exported via the apoplast. In order to elucidate the role of the different compartments with respect to sucrose metabolism, a yeast-derived invertase was directed into the cytosol and vacuole of transgenic tobacco plants. This was in addition to the targeting of yeast-derived invertase into the apoplast described previously. Vacuolar targeting was achieved by fusing an N-terminal portion (146 amino acids long) of the vacuolar protein patatin to the coding region of the mature invertase protein. Transgenic tobacco plants expressing the yeast-derived invertase in different subcellular compartments displayed dramatic phenotypic differences when compared to wild-type plants. All transgenic plants showed stunted growth accompanied by reduced root formation. Starch and soluble sugars accumulated in leaves indicating that the distribution of sucrose was impaired in all cases. Expression of cytosolic yeast invertase resulted in the accumulation of starch and soluble sugars in both very young (sink) and older (source) leaves. The leaves were curved, indicating a more rapid cell expansion or cell division at the upper side of the leaf. Light-green sectors with reduced photosynthetic activity were evenly distributed over the leaf surface. With the apoplastic and vacuolar invertase, the phenotypical changes induced only appear in older (source) leaves. The development of bleached and/or necrotic sectors was linked to the source state of a leaf. Bleaching followed the sink to source transition, starting at the rim of the leaf and moving to the base. The bleaching was paralleled by the inhibition of photosynthesis.","doi":"10.1111/j.1365-313x.1991.00095.x","pmid":"1844880"} +{"title":"Plant seeds contain several thioredoxins of regular size.","abstract":"Thioredoxin systems composed of several thioredoxin isoproteins and a NADPH: thioredoxin reductase are contained in the albumin-globulin fraction of wheat and soy-bean seed proteins. Two wheat thioredoxins I and II were separated on CM-cellulose whereas soy-bean extracts could be resolved into three thioredoxins I, II, and III on DEAE-cellulose. These proteins were purified to apparent homogeneity and were shown by sodium dodecylsulfate/polyacrylamide gel electrophoresis to possess the molecular weight Mr identical to 12000 typical of the single bacterial and animal thioredoxin. In contrast, gel filtration runs may yield erroneous estimates of thioredoxin molecular weights. The seed thioredoxins can serve as ribonucleotide reductase (Escherichia coli) substrates. They stimulate spinach NADP: malate dehydrogenase but are inactive towards chloroplast fructose-bisphosphatase. These results demonstrate that the number of thioredoxins in nongreen plant tissues approaches that of leaves; additional explanations must therefore be sought for the multiple thioredoxin profiles of plants besides diversification for light-dependent and light-independent functions.","doi":"10.1111/j.1432-1033.1983.tb07267.x","pmid":"6682037"} +{"title":"Synthesis of soybean agglutinin in bacterial and mammalian cells.","abstract":"The cDNA of soybean agglutinin (SBA), a glycoprotein lectin, obtained from the mRNA of soybean seeds at mid-maturation, was cloned in a lambda gt 10 phage and subcloned in a pUC-8 plasmid. Probing with a fragment of the lectin gene [Vodkin, L. O., Rhodes, P. R. & Goldberg, R. B. (1983) Cell 34, 1023-1031] afforded a clone of 1012 nucleotides containing the complete coding region of 858 nucleotides for the precursor to soybean agglutinin. The deduced amino acid sequence contains the 253 residues of the mature lectin and an hydrophobic N-terminal signal peptide of 32 amino acids. Expression in Escherichia coli of the cDNA coding for the precursor to the lectin or for the mature lectin led to the accumulation of large quantities of inclusion bodies, from which mature SBA was isolated in small yield (up to 1 mg/l). It was identical with the native lectin in the hemagglutinating activity and carbohydrate specificity, N-terminal sequence and oligomeric structure, but, because it was not glycosylated, its subunit mass was lower by 2 kDa. Our findings show that pre-SBA is processed into the mature form in the bacteria, and that, contrary to what has been suggested [Nagai, K. & Yamaguchi, H. (1993) J. Biochem. (Tokyo) 113, 123-125], glycosylation is not essential for the folding of the lectin, nor for its subunit assembly into a biologically active tetramer. To obtain recombinant SBA in secreted form, the pre-SBA cDNA was subcloned in pTM1 vector and the construct inserted into vaccinia virus. When monkey BS-C-1 cells were infected by the virus, using a double expression protocol, recombinant lectin was secreted into the growth medium, from which it was isolated by immunoaffinity chromatography at a yield similar to that from the bacteria. Except for its lower hemagglutinating activity, the product was indistinguishable from native SBA in all properties tested. It was also susceptible to digestion by endo-beta-N-acetylglucosaminidase H or N-glycanase which caused a decrease of 2 kDa in its subunit mass and gave the same results on lectin blot analysis, indicating that it too is a glycoprotein with a single oligomannose unit.","doi":"10.1111/j.1432-1033.1997.t01-3-00684.x","pmid":"9395314"} +{"title":"Effects of methotrexate on biopterin levels and synthesis in rat cultured pineal glands.","abstract":"Culture of rat pineal glands in methotrexate (0.5, 5, or 10 microM) for 6 or 24 h did not alter pineal tetrahydrobiopterin (85-90% of total biopterin in cultured glands), except for a decrease of 30% after 24 h culture in 10 microM methotrexate. However, pineal dihydrobiopterin and/or biopterin (10-15% of total biopterin) was increased by methotrexate up to 2.5-fold. Biopterin detected in the culture medium following pineal culture was also increased to a similar extent after methotrexate treatment and appeared to represent leakage of pineal dihydrobiopterin and/or biopterin. Culture of glands in 5 microM methotrexate did not alter the conversion of [U-14C]-guanosine to [14C]biopterin, suggesting that pineal tetrahydrobiopterin synthesis was not altered by methotrexate. Complete inhibition of dihydrofolate reductase activity measured in pineal homogenates was obtained following culture of glands in all concentrations of methotrexate studied. Therefore, dihydrofolate reductase and dihydrobiopterin do not appear to be involved in a major biosynthetic pathway for pineal tetrahydrobiopterin from GTP, although they may have a minor role in tetrahydrobiopterin synthesis.","doi":"10.1111/j.1471-4159.1984.tb12762.x","pmid":"6726234"} +{"title":"Stereospecific actions of 2,5-dimethoxy-4-methylamphetamine (DOM) on colonic temperature in the rat at various ambient temperatures.","abstract":"The R(-) and S(+)-isomers of 2,5-dimethoxy-4-methylamphetamine (DOM) produce a dose-dependent hypothermia in rats kept in the cold (6 degrees C). 2 This hypothermia was linearly dependent upon ambient temperature and the R(-)-isomer was considerably more potent than the S(+)-isomer. 3 A statistically significant tachyphylaxis was observed when R(-)-DOM was administered on two successive days. The response seven days after the second injection was similar to that on the first day of injection. 4 The hypothermia induced by R(-) and S(+)-DOM was antagonized by methysergide but not by p-chlorophenylalanine (PCPA) or pimozide. Methysergide, PCPA or pimozide alone did not elicit hypothermia at the doses used. The results indicate that R(-) and S(+)-DOM act at post-synaptic 5-hydroxytryptamine receptors.","doi":"10.1111/j.1476-5381.1976.tb10383.x","pmid":"134754"} +{"title":"Construction of gene expression system in cultured tobacco cells.","abstract":"To construct a gene expression system in cultured tobacco cells, useful regulatory elements of plant genes were studied. The promoter of the horseradish peroxidase gene, prxC2, showed high activity in tobacco cells, and it contained enhancer sequences and a cis element for wound induction. The heat shock promoter of the HSP18.2 gene from A. thaliana had strong activity of transcription when the incubation temperature of tobacco cells was shifted from 25 degrees C to 37 degrees C. These elements could be good candidates for foreign gene expression in tobacco cells.","doi":"10.1111/j.1749-6632.1996.tb40551.x","pmid":"8659929"} +{"title":"Peripherally administered reduced pterins do enter the brain.","abstract":"The content of tetrahydrobiopterin in rat brain was doubled by peripherally administered tetrahydrobiopterin, with the natural 1 diastereoisomer more effective than the unnatural d configuration. The model pteridine, 6-methyltetrahydropterin was ten times more efficient than tetrahydrobiopterin in crossing the blood-brain barrier, and striatal concentrations of 6-methyltetrahydropterin remained elevated for 2 hours, declining with a half-life of 3 hours. While no evidence for a specific uptake mechanism for concentrating 6-methyltetrahydropterin in cells containing tetrahydrobiopterin was detected, the pterin was found in ts presumed site of action, the nerve terminal. Replacement therapy with reduced pterins may therefore be effective in the treatment of the neurological disorders associated with the variant forms of hyperphenylalaninemia that result from defects in the biosynthesis or metabolism of tetrahydrobiopterin within the central nervous system.","doi":"10.1126/science.7233193","pmid":"7233193"} +{"title":"Infection of epithelial cells by pathogenic neisseriae reduces the levels of multiple lysosomal constituents.","abstract":"Members of our group reported recently that neisseria infection of human epithelial cells results in accelerated degradation of the major lysosomal integral membrane protein LAMP1 and that this is due to hydrolysis of this glycoprotein at its immunoglobulin A1 (IgA1)-like hinge by the neisseria type 2 IgA1 protease (L. Lin et al., Mol. Microbiol. 24:1083-1094, 1997). We also reported that the IgA1 protease plays a major role in the ability of the pathogenic neisseriae to survive within epithelial cells and hypothesized that this is due to alteration of lysosomes as a result of protease-mediated LAMP1 degradation. In this study, we tested the hypothesis that neisseria infection leads to multiple changes in lysosomes. Here, we report that neisseria infection also reduces the levels of three other lysosomal markers: LAMP2, lysosomal acid phosphatase (LAP), and CD63. In contrast, neither the epidermal growth factor receptor level nor the beta-tubulin level is affected. A detailed examination of LAMP2 indicated that the reduced LAMP2 levels are not the result of an altered biosynthetic rate or of cleavage by the IgA1 protease. Nevertheless, the protease plays a role in reducing LAMP2 and LAP activity levels, as these are partially restored in cells infected with an iga mutant. We conclude that neisseria infection results in multiple changes to the lysosomes of infected epithelial cells and that these changes are likely an indirect result of IgA1 protease-mediated cleavage of LAMP1.","doi":"10.1128/IAI.66.10.5001-5007.1998","pmid":"9746610"} +{"title":"Yeast Ran-binding protein 1 (Yrb1) shuttles between the nucleus and cytoplasm and is exported from the nucleus via a CRM1 (XPO1)-dependent pathway.","abstract":"The RanGTP-binding protein RanBP1, which is located in the cytoplasm, has been implicated in release of nuclear export complexes from the cytoplasmic side of the nuclear pore complex. Here we show that Yrb1 (the yeast homolog of RanBP1) shuttles between the nucleus and the cytoplasm. Nuclear import of Yrb1 is a facilitated process that requires a short basic sequence within the Ran-binding domain (RBD). By contrast, nuclear export of Yrb1 requires an intact RBD, which forms a ternary complex with the Xpo1 (Crm1) NES receptor in the presence of RanGTP. Nuclear export of Yrb1, however, is insensitive towards leptomycin B, suggesting a novel type of substrate recognition between Yrb1 and Xpo1. Taken together, these data suggest that ongoing nuclear import and export is an important feature of Yrb1 function in vivo.","doi":"10.1128/MCB.20.12.4295-4308.2000","pmid":"10825193"} +{"title":"Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.","abstract":"The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke.","doi":"10.1128/iai.34.1.11-15.1981","pmid":"6271676"} +{"title":"Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin.","abstract":"Expression of inducible nitric oxide (NO) synthase has been shown to inhibit the development of several pathogens, including fungi, bacteria, parasites, and viruses. However, there is still controversy as to whether this effector mechanism can inhibit the development of human pathogens. We now report that gamma interferon (IFN-gamma) induces the elimination of Plasmodium falciparum-infected primary human hepatocytes from cultures and that the antimalarial activity is dependent on NO. Infection with the parasite alone in the absence of added IFN-gamma caused a 10-fold increase in NO formation. Both spontaneous inhibition and IFN-gamma-induced inhibition of Plasmodium yoelii-infected murine hepatocytes were increased with the addition of the NO synthase cofactor tetrahydrobiopterin, or sepiapterin, which is converted to tetrahydrobiopterin. These results indicate that under in vitro conditions the parasite itself provides a signal that triggers induction of the NO pathway in human and murine hepatocytes and that NO formation in infected hepatocytes is limited by tetrahydrobiopterin availability.","doi":"10.1128/iai.62.9.4043-4046.1994","pmid":"8063424","reference_id":"27328851"} +{"title":"Small nuclear RNA genes transcribed by either RNA polymerase II or RNA polymerase III in monocot plants share three promoter elements and use a strategy to regulate gene expression different from that used by their dicot plant counterparts.","abstract":"RNA polymerase (Pol) II- and RNA Pol III-transcribed small nuclear RNA (snRNA) genes of dicotyledonous plants contain two essential upstream promoter elements, the USE and TATA. The USE is a highly conserved plant snRNA gene-specific element, and its distance from the -30 TATA box, corresponding to approximately three and four helical DNA turns in Pol III and Pol II genes, respectively, is crucial for determining RNA Pol specificity of transcription. Sequences upstream of the USE play no role in snRNA gene transcription in dicot plants. Here we show that for expression of snRNA genes in maize, a monocotyledonous plant, the USE and TATA elements are essential, but not sufficient, for transcription. Efficient expression of both Pol II- and Pol III-specific snRNA genes in transfected maize protoplasts requires an additional element(s) positioned upstream of the USE. This element, named MSP (for monocot-specific promoter; consensus, RGCCCR), is present in one to three copies in monocot snRNA genes and is interchangeable between Pol II- and Pol III-specific genes. The efficiency of snRNA gene expression in maize protoplast is determined primarily by the strength of the MSP element(s); this contrasts with the situation in protoplasts of a dicot plant, Nicotiana plumbaginifolia, where promoter strength is a function of the quality of the USE element. Interestingly, the organization of monocot Pol III-specific snRNA gene promoters closely resembles those of equivalent vertebrate promoters. The data are discussed in the context of the coevolution of Pol II- and Pol III-specific snRNA gene promoters within many eukaryotic organisms.","doi":"10.1128/mcb.14.9.5910-5919.1994","pmid":"8065324","reference_id":"27330750"} +{"title":"Urine neopterin: a new parameter for serial monitoring of disease activity in patients with systemic lupus erythematosus.","abstract":"This study provides initial evidence that changes in urine concentrations of neopterin are significantly correlated with fluctuations in disease activity over time, scored using the BILAG index, amongst individual patients with SLE. Consequently, serial urine neopterin measurements appear to be clinically useful for monitoring disease activity and may contribute substantially to therapeutic decision making in these patients.","doi":"10.1136/ard.53.11.743","pmid":"7826135"} +{"title":"Experimental evidence of a plant meridian system: I. Bioelectricity and acupuncture effects on electrical resistance of the soybean (Glycine max).","abstract":"Experiments were conducted on the bioelectrical potential and resistance of soybean (Glycine max) roots, stems, leaves and pods. Results showed a higher potential and lower electrical resistance associated with the leaf cushion, main vein and small vein areas in comparison with other parts of the plant. When two needles were inserted into one of the low resistance points, i.e., the leaf cushion area, the electrical resistance decreased 26.0% on the main vein and 4.5% on the mesophyll of the soybean leaf for at least 5 hours after acupuncture. These characteristics, similar to those of meridian transmission lines in humans and other animals, suggest that a meridian system might also exist in plants.","doi":"10.1142/S0192415X94000024","pmid":"8030614"} +{"title":"Glutathione removal reveals kinases as common targets for K-Cl cotransport stimulation in sheep erythrocytes.","abstract":"K-Cl cotransport is activated by swelling, lowering of cellular free Mg (Mgi), and thiol modification of erythrocytes. Direct actions by thiol reagents on the K-Cl cotransport complex were separated from indirect effects through nonoxidative changes in cellular glutathione (GSH). We used 1-chloro-2,4-dinitrobenzene (CDNB), which, conjugated to GSH, is extruded from the erythrocyte as a thioether. CDNB caused a small biphasic effect (inhibition and stimulation) on K-Cl cotransport and, at 1 mM, abolished its stimulation by N-ethylmaleimide (NEM), diazenedicarboxylic acid bis[N,N-dimethylamide], methyl methanethiosulfonate, and staurosporine, a kinase inhibitor, independent of the order of treatment. Hence, NEM and other activating-thiol reagents, and perhaps GSH removal itself, target unidentified kinases involved in activation of K-Cl cotransport. CDNB also abrogated K-Cl cotransport stimulation by Mgi depletion independent of the order of treatment, indicating inhibition at a second site nearer to the transporter. Furthermore, CDNB treatment elevated and rendered K-Cl cotransport insensitive to osmotic shrinkage, suggesting uncoupling from the regulator.","doi":"10.1152/ajpcell.1995.269.1.C234","pmid":"7631750"} +{"title":"Phosphorylation of calponin in airway smooth muscle.","abstract":"Calponin is an actin-binding protein known to be a substrate in vitro for several protein kinases and phosphoprotein phosphatases. We tested the hypothesis that calponin is phosphorylated in vivo using canine tracheal smooth muscle strips metabolically labeled with 32Pi. Calponin was gel purified from muscles stimulated with 1 microM carbachol. Phosphorylation increased to 2.0 times the basal level of 178 +/- 26 counts per minute (cpm)/microgram calponin within 30 s to 350 +/- 64 cpm/micrograms. Two-dimensional nonequilibrium pH gradient gel electrophoresis resolved four charge isoforms of calponin in unstimulated muscle. Stimulation with carbachol induced an additional more acidic isoform. Phosphorylation of calponin in vitro with protein kinase C (PKC) also induced formation of additional acidic isoforms. The functional effect of phosphorylation was demonstrated using an in vitro motility assay in which unphosphorylated calponin (2 microM) caused a profound inhibition of actin sliding. Calponin phosphorylated by PKC did not inhibit actin sliding. The results show that phosphorylation of calponin occurs in intact tracheal smooth muscle and that phosphorylation of calponin in vitro alleviates the inhibitory effect of calponin on actomyosin function.","doi":"10.1152/ajplung.1997.272.1.L115","pmid":"9038910"} +{"title":"Safety, tolerance and pharmacokinetics of 2.0 g cefpirome (HR 810) after single and multiple dosing.","abstract":"After intravenous injection of a single dose of 2.0 g cefpirome (HR 810) and multiple doses of 2.0 g b.i.d. (11 doses) to 10 healthy male volunteers in an open design, concentrations of unchanged drug were measured at various times in serum and urine over 24 and 96 h, respectively. Cefpirome concentrations were determined using high-pressure liquid chromatography (HPLC). The biological half-life (t1/2, beta) found by fitting a two-compartment open model to the data was 2 h. No accumulation of the serum levels could be detected during the multiple-dose phase. Urinary concentrations of unchanged cefpirome effective against most clinically relevant bacteria were detected for at least 36 h. The drug was safe and well tolerated. No drug-related changes were observed for blood pressure, heart rate, ECG, haematology, clinical chemistry or urinalysis, including beta 2-microglobulin in serum and creatinine clearance.","doi":"10.1159/000238594","pmid":"3180904"} +{"title":"Linear IgA disease: cylindroma demonstrates heterogeneity of the target antigens.","abstract":"Serum from 58 patients with linear IgA disease was tested by indirect immunofluorescence on the novel substrate cylindroma, which produces an abundance of basement membrane components. The use of split skin and of cylindroma has identified 2 target antigens. The majority of patients have a target antigen associated with epidermal cells and similar in distribution on cylindroma to hemidesmosome proteins. A minority have a dermal antigen with the distribution of collagen VII on cylindroma. These data support the hypothesis that linear IgA disease is a heterogeneous disease with regard to the target antigens.","doi":"10.1159/000246944","pmid":"8049543","reference_id":"27315061"} +{"title":"Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic test.","abstract":"To determine if there is abnormal phenylalanine and biopterin metabolism in patients with dopa-responsive dystonia (DRD), we measured plasma levels of phenylalanine, tyrosine, biopterin, and neopterin at baseline, and 1, 2, 4, and 6 hours after an oral phenylalanine load (100 mg/kg). Seven adults with DRD, two severely affected children with DRD, and nine adult controls were studied. All patients had phenylalanine and tyrosine concentrations within the normal range at baseline. In the adult patients, phenylalanine levels were higher than in controls at 2, 4, and 6 hours post-load (p < 0.0005); tyrosine concentrations were lower than control levels at 1, 2, and 4 hours post-load (p < 0.05). Phenylalanine to tyrosine ratios were elevated in patients at all times post-load (p < 0.0005). Biopterin levels in the patients were decreased at baseline and 1, 2, and 4 hours post-load (p < 0.005). Pretreatment with tetrahydrobiopterin (7.5 mg/kg) normalized phenylalanine and tyrosine profiles in two adult patients. In the children with DRD, phenylalanine to tyrosine ratios were slightly elevated at baseline. Following phenylalanine loading, the phenylalanine profiles were similar to those seen in the adult patients but there was no elevation in plasma tyrosine. Baseline biopterin levels were lower in the children with DRD than in the adult patients or the controls and there was no increase in biopterin post-load. In both the children and adults with DRD, neopterin concentrations did not differ from control values at baseline or after phenylalanine load. The results are consistent with decreased liver phenylalanine hydroxylase activity due to defective synthesis of tetrahydrobiopterin in patients with DRD. The findings show that a phenylalanine load may be useful in the diagnosis of this disorder.","doi":"10.1212/wnl.48.5.1290","pmid":"9153460"} +{"title":"California's tobacco tax initiative: the development and passage of Proposition 99.","abstract":"In this case study, we describe and analyze the development and passage of California's tobacco tax initiative, Proposition 99, the Tobacco Tax and Health Promotion Act of 1988. We gathered information from published reports, public documents, personal correspondence, internal memorandums, polling data, and interviews with representatives from organizations that participated in the Proposition 99 campaign. Proposition 99 passed as a result of the efforts of a coalition of voluntary health agencies, medical organizations, and environmental groups. They organized a long-term effort by conducting essential polling, planning strategies, gaining media exposure, developing a coalition, and running a successful campaign to enact the tax by shifting the venue from legislative to initiative politics. To build the coalition that was needed to pass Proposition 99, public health proponents enlisted the help of medical organizations in exchange for additional revenue to be allocated to medical services. By shifting the venue from the legislature to the general public, advocates capitalized on public concern about tobacco and for youth and took advantage of the tobacco industry's low credibility. The passage of Proposition 99, despite a massive campaign against it by the tobacco industry, represents a milestone in the tobacco control and public health fields. From its passage in 1988 through 1993, tobacco use in California declined by 27 percent, which is three times faster than the United States average. As a result, Proposition 99 has served as a national model for other states and the federal government. Although allocation of tobacco tax revenues specifically to health education and prevention was a primary goal during the development and passage of Proposition 99, when the venue shifted back to the legislature for implementation, medical organizations successfully advocated illegal diversions of Proposition 99 tobacco control and research funds to medical services. Organizations seeking to enact Proposition 99-like tobacco tax increases must be prepared to mount aggressive campaigns to pass the initiative in the face of major tobacco industry opposition and then must continue to work to protect the program after passage by voters.","doi":"10.1215/03616878-21-3-543","pmid":"8784688"} diff --git a/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c003.json b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c003.json new file mode 100644 index 0000000..954aaa2 --- /dev/null +++ b/data/abstracts/msd-arch/part-00195-6787be90-eb7f-4950-8ef0-98d9dbbbcd38-c003.json @@ -0,0 +1,10 @@ +{"title":"Purification of alginate oligosaccharides with root growth-promoting activity toward lettuce.","abstract":"Sodium alginate was degraded by alginate lyase from Corynebacterium sp., and the product was purified by an ultrafiltration (UF) membrane module. The UF treatment was carried out at a transmembrane pressure of 0.15 MPa and a flow velocity of 0.6 m/s in the cross-flow mode, and non-degraded alginate was almost completely removed. The alginate oligosaccharide obtained was a mixture of di- to octasaccharides and had promoting activity toward lettuce root elongation (about 2-fold compared with the control) in the concentration range of 200-3000 microg/ml. The effect of the degree of polymerization on this activity was examined by using each oligosaccharide fractionated by gel chromatography. The tri-, tetra-, penta- and hexasaccharides were each found to have root growth-promoting activity in a lettuce bioassay.","doi":"10.1271/bbb.64.1067","pmid":"10879484"} +{"title":"Effect of nicotine on type 2 deiodinase activity in cultured rat glial cells.","abstract":"Intracellular generation of triiodothyronine (T3) from thyroxine (T4) by type 2 deiodinase (D2) in the mammalian brain, plays a key role in thyroid hormone action. The presence of D2 in rat astrocytes suggests the importance of glial cells in the regulation of intracellular T3 levels in the rat central nervous system (CNS). To analyze further the factors that regulate D2 activity in the CNS, we investigated the effects of nicotine and of mecamylamine, which inhibits the binding of nicotine with nicotinic acetylcholine receptors, on D2 activity in cultured mixed glial cells of the rat brain. We incubated cultured mixed glial cells obtained from neonatal Wistar rats in the presence of 10 mM dithiothreitol, 2 nM [125I] reverse T3 and 1 mM 6-N-propyl-2-thiouracil for 2 h at 37 degrees C, and the released 125I- was counted in a gamma counter. D2 activity of cultured cells was dependent on the temperature and the amount of protein. The basal D2 activity of rat mixed glial cells was 1.9 +/- 0.2 fmol of I- released/mg protein/h (mean +/- SEM). The addition of 10(-11), 2 x 10(-11), 10(-10), and 10(-9) M nicotine significantly increased D2 activity to approximately 2.2-, 2.4, 3.5- and 2.9-fold the basal level, respectively. D2 activity stimulated by 10(-8) M nicotine (2.5-fold) reached a peak after 9 h incubation. The stimulatory effect of nicotine was completely blocked by 10(-6) M mecamylamine. In conclusion, nicotine increases D2 activity probably via nicotinic acetylcholine receptors, and may influence brain function, at least in part, by affecting thyroid hormone metabolism.","doi":"10.1507/endocrj.46.107","pmid":"10426574"} +{"title":"Thyroid functions before and after maintenance hemodialysis in patients with chronic renal failure.","abstract":"To study the factors involved in the low thyroid hormone levels in patients with chronic renal failure (CRF), we investigated thyroid functions just before and after hemodialyses (HD) in 32 such patients who were on maintenance HD. In addition, we measured serum thyroid hormone binding inhibitor activities (THBI) in another set of 37 patients. None of the patients had been suspected of having thyroid diseases. HD duration and aging did not have a significant effect on the results of the thyroid function tests. Before each HD, the serum concentrations of T3, T4, FT3, FT4, rT3, PBI, FT3I, FT4I, FT3/T3, FT4/T4, T4/TBG, T4/TSH and FT4/TSH were lower, and those of TSH, TBG, and thyroglobulin (Tg) were higher in the patients than in normal controls. The thyroid hormone concentrations were negatively correlated with the BUN and creatinine levels. The Tg levels were positively correlated with the BUN levels. After each HD, almost all the thyroid function tests including T4/TBG ratio showed improvements, which indicated that hemodilution and a decrease in the T4-binding affinity of TBG with thyroid hormones were the major factors in the low thyroid hormone levels in CRF patients. However, even after HD, T3, FT3, rT3, T4/TSH and FT4/TSH were still lower and TSH and Tg were still higher in the patients. These data suggested that the CRF patients were in a subclinical hypothyroid state. THBI was high in patients with CRF and did not change following HD. NEFA did not seem to contribute to the high THBI before HD, because they were in the normal range. However, as NEFA became very high after HD and possessed THBI, we calculated the corrected THBI (C-THBI) by subtracting the effect of NEFA from total THBI. C-THBI was high before HD and decreased after HD. Therefore, it was suggested that this C-THBI contributed to the abnormalities in the affinity of TBG with thyroid hormones. From these studies, it is concluded that (1) the patients with CRF may be in a subclinical hypothyroid state, although hemodilution was seen to have a strong effect on the thyroid hormone concentrations, and (2) C-THBI may have an effect on the affinity of TBG with thyroid hormones and play an additional role in low thyroid hormone levels in these patients. The mechanisms of hypothyroidism and the nature of C-THBI remain to be clarified.","doi":"10.1507/endocrj1954.35.865","pmid":"3250862"} +{"title":"Clinical trials of cefpodoxime proxetil suspension in paediatrics.","abstract":"The pharmacokinetics, bacteriological and clinical efficacy, and safety of the suspension formulation of cefpodoxime proxetil, an oral cephalosporin antibacterial, were evaluated in paediatric patients with various infections. With single doses of 3 and 6 mg/kg (cefpodoxime equivalent) a dose response was evident in the serum concentration values. Absorption, as evidenced by serum concentrations and areas under the concentration-time curve, was enhanced when the suspension was administered before a meal. The overall clinical efficacy (defined as an excellent or good response) in evaluable patients (those from whom a pathogen was isolated) was 94.7% (451 of 476). Bacteriological eradication rates were as follows: Gram-positive bacteria 91.3%; Gram-negative bacteria 88.6%, and 90.0% overall. Side effects occurred in 17 (2.29%) patients, and transient and reversible abnormal laboratory values were found in a few patients.","doi":"10.2165/00003495-199100423-00011","pmid":"1726209"} +{"title":"Effects of zinc-treated soybean meal on ruminal fermentation and intestinal amino acid flows in steers fed corn silage-based diets.","abstract":"The objectives of this study were to examine the effects of feeding zinc-treated soybean meal (Zn-SBM) on ruminal fermentation patterns and duodenal AA flows in steers fed diets based on corn silage and corn. Six steers (385 kg) fitted with ruminal, duodenal, and ileal cannulas were used in a replicated 3 x 3 Latin square design experiment with 14-d periods. Diets were supplemented with solvent-extracted soybean meal (SBM), Zn-SBM, or a 50:50 combination (CP basis) of SBM:Zn-SBM. Ruminal escape N content of SBM and Zn-SBM were 30.0 and 57.0%, respectively, based on 12-h Dacron bag incubation. Protein sources provided approximately 30% of total CP in diets containing 12.6% CP (DM basis). Dry matter intake was equalized throughout the study at 2.2% of average initial BW. Total N flow at the duodenum was similar (P = .47) among treatments, but a trend (P = .15) for increased nonmicrobial N flow occurred when SBM and Zn-SBM were fed in combination. Micobial N flow and true efficiency of microbial CP synthesis were not affected by treatment (P = .87 and .37, respectively). Ruminal fermentation characteristics generally were unaffected (P > .10) by protein source. A positive quadratic response (P < .06) was observed for total and essential AA flows to the small intestine because flows of total and essential AA from ruminally undegraded dietary protein tended (P = .12) to increase when SBM and Zn-SBM were fed in combination. Absorption of AA from the small intestine also showed a positive quadratic (P < .06) response for SBM:Zn-SBM. Microbial AA flow to the small intestine was similar (P = .87) among treatments.(ABSTRACT TRUNCATED AT 250 WORDS)","doi":"10.2527/1993.71123423x","pmid":"8294296"} +{"title":"The relationship among dietary undetermined anion, acid-base balance, and nutrient metabolism in swine.","abstract":"Dietary undetermined anion (dUA) reflects, in part, the net acid load contributed by the diet. Although dUA is known to influence performance and nutrient metabolism of swine, a lack of knowledge impairs its application to diet formulation. This study was undertaken to separate the effects of dUA from the individual electrolytes that constitute its calculation. Eighteen 35-kg pigs were fitted with indwelling venous catheters and fed one of three barley and soybean meal-based diets: a control diet (C), an acidogenic diet containing calcium chloride (A), or a compensated acidogenic diet containing alkaline salts of sodium and potassium, as well as calcium chloride (CA). Compared with diet C, diet A lowered (P < .05) blood pH, bicarbonate, and base excess and increased (P < .05) urinary ammonium, titratable acid (TA), and net acid excretion (NAE). Diet CA returned blood acid-base values to normal and reduced urinary ammonium, TA, and NAE relative to diet A. Total nitrogen balance was unaffected by diet. Diet CA increased (P < .05) water intake and urine output. Diet A, but not CA, increased (P < .05) serum ionized Ca and C1. Apparent Ca and S digestibility and retention were reduced by diet A, but not by CA. Sodium retention was enhanced (P < .05) by diets A and CA; potassium retention was impaired (P < .05) by CA. Dietary UA altered systemic and renal acid-base balance in pigs. Mineral, but not nitrogen, metabolism was affected by both dUA and specific ion effects.","doi":"10.2527/1997.7592445x","pmid":"9303463"} +{"title":"Abuse of smoking methamphetamine mixed with tobacco. III. Urinary metabolites of N-cyanomethylmethamphetamine, a pyrolysis product formed by smoking methamphetamine in tobacco, and species difference in its metabolism between rat and mouse.","abstract":"1. N-cyanomethylmethamphetamine (CMMA) or methamphetamine (MA) was given intraperitoneally to rat and mouse (1, 3, 10 mg/kg). The basic urinary metabolites of CMMA were determined by mass spectrometry (MS) and compared with those of MA. 2. N-formylmethamphetamine (FMA), a specific metabolite of CMMA, was found in both rat and mouse urine. However, the dose percentage of FMA excreted in mouse urine was less than one-quarter of that in rat urine. 3. No CMMA was detected in rat or mouse urine collected within 72 h after dosing. All other basic metabolites of CMMA except FMA, i.e. MA, amphetamine (AP), p-hydroxymethamphetamine (OHMA) and p-hydroxyamphetamine (OHAP), were the same as those of MA in both species. 4. The excretion pattern of the urinary metabolites of CMMA was similar to that of MA except FMA in both species, though the amount of each metabolite of MA administration was larger than that of CMMA administration. However, in urinary excretion of FMA and hydroxylated metabolites, definite species differences were observed between rat and mouse. 5. A trace amount of FMA was identified in the urine of an abuser who had smoked MA with tobacco.","doi":"10.3109/00498259509061832","pmid":"7604606"} +{"title":"Maternal autoimmune response to recombinant Ro/SSA and La/SSB proteins in Japanese neonatal lupus erythem atosus.","abstract":"In the majority of Japanese infants with NLE, maternal anti-Ro/SSA autoimmune response was directed against both of 60-kd and 52-kd recombinant Ro/SSA proteins. There was no profile of anti-Ro/SSA and La/SSB response unique to mothers of children with CHB or cutaneous manifestations of NLE.","doi":"10.3109/08916939509001947","pmid":"8852519"} +{"title":"Plasma Na+-K+ ATPase inhibitory activity in normal and hypertensive subjects: relationship to intracellular electrolytes and blood pressure.","abstract":"The ability of plasma extracts to inhibit Na+-K+ ATPase in vitro (P.I.A.) was tested in 20 normotensives, 10 without (F-) and 10 with (F+) familial hypertension, in 20 borderlines (BL) and in 21 essential hypertensives (EH). In these subjects we also measured intralymphocytic sodium (ILSC) and potassium (ILKC) content, P.R.A. urinary aldosterone and Na+(Na+u), and blood pressure. P.I.A. of EH, BL and F+ subjects was significantly higher than that of F-. 60% of EH and BL and 40% of F+ had P.I.A. values greater than the highest found in F-. P.I.A. was significantly related to mean blood pressure (r = 0.63), to ILSC (r = 0.56), to ILKC (r = -0.56), to ILSC/ILKC ratio (r = 0.71) and to Na+u (r = 0.39) but not to P.R.A. or aldosterone. These data demonstrate that plasma extracts from young subjects prone to hypertension may inhibit sodium pump and that this inhibitor may affect blood pressure by altering the Na+/K+ intracellular ratio.","doi":"10.3109/10641968509077224","pmid":"2990769"} +{"title":"Fatigability of motor units estimated by changes in work performed during their repetitive stimulation during the fatigue test.","abstract":"In numerous studies resistance to fatigue is evaluated by measuring the peak tension of motor units in muscle. In the present study, the work performed within successive tetani during the fatigue test of rat medial gastrocnemius motor units was estimated by assessing of the area under the tension record. Resistance to fatigue was evaluated by a modified fatigue index which is expressed as the ratio of the area under a tetanus recorded two minutes after maximal potentiation of tension has been reached to the area under this maximally potentiated tetanus. The values of this modified fatigue index were compared to the standard fatigue index which was taken as the ratio of peak tensions for corresponding tetani. For fast fatigable units, values of the modified fatigue index were significantly lower than those of the standard index. This observation resulted from changes in the shape of unfused tetani accompanying developing fatigue. These changes strongly influenced the area under the tension record whereas the peak tension of these tetani diminished less significantly. For slow and a part of fast resistant to fatigue units (with the standard fatigue index above 0.85) the modified fatigue index was slightly higher than the standard one although the difference was not significant. This phenomenon was due to the prolongation of relaxation which was visible in the last part of the fatigue test. It is being concluded that the modified fatigue index describes more precisely the fatigue-induced changes in tetani during the fatigue test than the standard fatigue index, especially in fast fatigable units.","doi":"10.55782/ane-1999-1294","pmid":"10230075"} diff --git a/llm_semantic_annotator/abstract/abstract_manager.py b/llm_semantic_annotator/abstract/abstract_manager.py index a46431e..438ec6e 100644 --- a/llm_semantic_annotator/abstract/abstract_manager.py +++ b/llm_semantic_annotator/abstract/abstract_manager.py @@ -116,7 +116,11 @@ def get_ncbi_abstracts_from_api(self): print(f"Total abstract :{abstract_count}") - def get_ncbi_abstracts_from_file(self): + def get_ncbi_abstracts_from_files(self): + + if 'json_files' not in self.config['from_file']: + return + files_to_parse = self.config['from_file']['json_files'] file_index = self._get_index_abstract() @@ -126,13 +130,37 @@ def get_ncbi_abstracts_from_file(self): continue self._link_to_json_file_with_index(file, file_index) file_index+=1 + + def get_ncbi_abstracts_from_directory(self): + import glob + + if 'json_dir' not in self.config['from_file']: + return + + directory_to_parse = self.config['from_file']['json_dir'] + file_index = self._get_index_abstract() + + for file in glob.glob(os.path.join(directory_to_parse, "*.json")): + self._link_to_json_file_with_index(file, file_index) + file_index+=1 - def _set_embedding_abstract_file(self): for filename in os.listdir(self.config['retention_dir']): if filename.startswith('abstracts_') and filename.endswith('.json'): - results = load_results(os.path.join(self.config['retention_dir'], filename)) + json_f = os.path.join(self.config['retention_dir'], filename) + try: + results = load_results(json_f) + except Exception as e: + results = [] + + with open(json_f, 'r') as fichier: + for ligne in fichier: + # Charger chaque ligne comme un dictionnaire JSON + dictionnaire = json.loads(ligne) + results.append(dictionnaire) + continue + genname = filename.split('.json')[0] self.mem.save_pth(self.mem.encode_abstracts(results,genname),genname) @@ -142,14 +170,11 @@ def manage_abstracts(self): if 'from_ncbi_api' in self.config : self.get_ncbi_abstracts_from_api() - else: - print("No abstracts source 'from_api' selected") - + if 'from_file' in self.config : - self.get_ncbi_abstracts_from_file() - else: - print("No abstracts source 'from_file' selected") - + self.get_ncbi_abstracts_from_files() + self.get_ncbi_abstracts_from_directory() + self._set_embedding_abstract_file() From 5dbab2f80309d67ac6790db9ea2642893a79e657 Mon Sep 17 00:00:00 2001 From: Olivier Filangi Date: Tue, 22 Oct 2024 16:40:04 +0200 Subject: [PATCH 2/6] bug fix with abstract formation --- llm_semantic_annotator/abstract/abstract_manager.py | 11 +++++++++-- .../similarity/model_embedding_manager.py | 6 +++++- 2 files changed, 14 insertions(+), 3 deletions(-) diff --git a/llm_semantic_annotator/abstract/abstract_manager.py b/llm_semantic_annotator/abstract/abstract_manager.py index 438ec6e..d14614e 100644 --- a/llm_semantic_annotator/abstract/abstract_manager.py +++ b/llm_semantic_annotator/abstract/abstract_manager.py @@ -149,8 +149,17 @@ def _set_embedding_abstract_file(self): if filename.startswith('abstracts_') and filename.endswith('.json'): json_f = os.path.join(self.config['retention_dir'], filename) + genname = filename.split('.json')[0] + pth_filename = self.mem.get_filename_pth(genname) + if os.path.exists(pth_filename): + print(f"{pth_filename} already exists !") + continue try: results = load_results(json_f) + # fix bug if abstracts is a dict + if isinstance(results, dict): + results = [results] + except Exception as e: results = [] @@ -160,8 +169,6 @@ def _set_embedding_abstract_file(self): dictionnaire = json.loads(ligne) results.append(dictionnaire) continue - - genname = filename.split('.json')[0] self.mem.save_pth(self.mem.encode_abstracts(results,genname),genname) def manage_abstracts(self): diff --git a/llm_semantic_annotator/similarity/model_embedding_manager.py b/llm_semantic_annotator/similarity/model_embedding_manager.py index 2bdeea2..9af645f 100644 --- a/llm_semantic_annotator/similarity/model_embedding_manager.py +++ b/llm_semantic_annotator/similarity/model_embedding_manager.py @@ -229,10 +229,14 @@ def encode_abstracts(self,abstracts,genname) : chunks_toencode = [] chunks_doi_ref = [] lcount = 0 - print("Flat abstracts to build batch.....") + + print("Flat abstracts to build batch.....",genname) for item in tqdm(abstracts): if 'abstract' in item and item['abstract'].strip() != '': if 'title' in item and item['title'].strip() != '': + if 'doi' not in item: + print(f"doi not found : {item['title']}") + continue sentences = re.split(r'(?<=[.!?])\s+(?=[A-Z])', item['abstract']) # title chunks_doi_ref.append(item['doi']) From e8d799aa9cb5c0c88b624a6434a5028f0bad2872 Mon Sep 17 00:00:00 2001 From: Olivier Filangi Date: Tue, 22 Oct 2024 18:41:16 +0200 Subject: [PATCH 3/6] add command build forum dataset --- config/msd_spark.json | 2 +- exec.sh | 14 +-- llm_semantic_annotator/__init__.py | 3 +- llm_semantic_annotator/__main__.py | 8 +- .../abstract/abstract_manager.py | 86 ++++++++++++++----- llm_semantic_annotator/core.py | 8 +- .../misc/scientific_abstract_rdf_annotator.py | 3 +- 7 files changed, 90 insertions(+), 34 deletions(-) diff --git a/config/msd_spark.json b/config/msd_spark.json index 39b1b2f..20415a5 100644 --- a/config/msd_spark.json +++ b/config/msd_spark.json @@ -45,7 +45,7 @@ "populate_abstract_embeddings" : { "abstracts_per_file" : 500, "from_file" : { - "json_dir" : "data/abstracts/msd-arch" + "json_dir" : "data/msd/export-pubmed-20241014-4-planetome-tagging-sub-test" } } } diff --git a/exec.sh b/exec.sh index a7fdee5..e81d868 100755 --- a/exec.sh +++ b/exec.sh @@ -36,8 +36,9 @@ execute_command() { 3) run_command python3 -m llm_semantic_annotator "$conffile" populate_abstract_embeddings ;; 4) run_command python3 -m llm_semantic_annotator "$conffile" compute_tag_chunk_similarities ;; 5) run_command python3 -m llm_semantic_annotator "$conffile" display_summary ;; - 6) run_command python3 -m llm_semantic_annotator "$conffile" build_graph ;; - 7) run_command python3 -m llm_semantic_annotator "$conffile" evaluate_encoder ;; + 6) run_command python3 -m llm_semantic_annotator "$conffile" build_rdf_graph ;; + 7) run_command python3 -m llm_semantic_annotator "$conffile" build_dataset_abstracts_annotations ;; + 8) run_command python3 -m llm_semantic_annotator "$conffile" evaluate_encoder ;; *) echo "Invalid option" ;; esac } @@ -53,8 +54,9 @@ echo "4. populate_abstract_embeddings" echo "5. compute similarities between tags and chunks abstracts" echo "6. display similarities information" echo "7. build turtle knowledge graph" -echo "8. evaluate encoder with mesh descriptors (experimental)" -read -p "Enter your choice (1-8): " choice +echo "8. build dataset abstracts annotations" +echo "9. evaluate encoder with mesh descriptors (experimental)" +read -p "Enter your choice (1-9): " choice case $choice in 1) @@ -62,10 +64,10 @@ case $choice in #run_command python3 -m llm_semantic_annotator "$conffile" populate_ncbi_taxon_tag_embeddings run_command python3 -m llm_semantic_annotator "$conffile" populate_abstract_embeddings run_command python3 -m llm_semantic_annotator "$conffile" compute_tag_chunk_similarities - run_command python3 -m llm_semantic_annotator "$conffile" build_graph + run_command python3 -m llm_semantic_annotator "$conffile" build_rdf_graph run_command python3 -m llm_semantic_annotator "$conffile" display_summary ;; - 2|3|4|5|6|7|8) + 2|3|4|5|6|7|8|9) execute_command $((choice - 1)) ;; *) diff --git a/llm_semantic_annotator/__init__.py b/llm_semantic_annotator/__init__.py index 698d865..2f9193f 100644 --- a/llm_semantic_annotator/__init__.py +++ b/llm_semantic_annotator/__init__.py @@ -21,6 +21,7 @@ from .core import main_compute_tag_chunk_similarities from .core import main_display_summary from .core import main_build_graph - +from .core import main_build_dataset_abstracts_annotation from .core import get_scores_files + from .similarity_evaluator import similarity_evaluator_main \ No newline at end of file diff --git a/llm_semantic_annotator/__main__.py b/llm_semantic_annotator/__main__.py index f3e10b4..db40b14 100644 --- a/llm_semantic_annotator/__main__.py +++ b/llm_semantic_annotator/__main__.py @@ -9,6 +9,7 @@ from llm_semantic_annotator import similarity_evaluator_main from llm_semantic_annotator import main_display_summary from llm_semantic_annotator import main_build_graph +from llm_semantic_annotator import main_build_dataset_abstracts_annotation from rich import print import argparse @@ -40,7 +41,8 @@ def parse_arguments(): "populate_abstract_embeddings", "compute_tag_chunk_similarities", "display_summary", - "build_graph", + "build_rdf_graph", + "build_dataset_abstracts_annotations", "evaluate_encoder"], help="Type d'exécution à effectuer." ) @@ -74,8 +76,10 @@ def main(): main_compute_tag_chunk_similarities(config) elif args.execution_type == "display_summary": main_display_summary(config) - elif args.execution_type == "build_graph": + elif args.execution_type == "build_rdf_graph": main_build_graph(config) + elif args.execution_type == "build_dataset_abstracts_annotations": + main_build_dataset_abstracts_annotation(config) elif args.execution_type == "evaluate_encoder": similarity_evaluator_main(config) else: diff --git a/llm_semantic_annotator/abstract/abstract_manager.py b/llm_semantic_annotator/abstract/abstract_manager.py index d14614e..2361785 100644 --- a/llm_semantic_annotator/abstract/abstract_manager.py +++ b/llm_semantic_annotator/abstract/abstract_manager.py @@ -4,6 +4,7 @@ from llm_semantic_annotator import load_results import xml.etree.ElementTree as ET from pathlib import Path +import pandas as pd class AbstractManager: def __init__(self, config, model_embedding_manager): @@ -143,6 +144,24 @@ def get_ncbi_abstracts_from_directory(self): for file in glob.glob(os.path.join(directory_to_parse, "*.json")): self._link_to_json_file_with_index(file, file_index) file_index+=1 + + def _get_data_abstracts_file(self,json_f): + try: + results = load_results(json_f) + # fix bug if abstracts is a dict + if isinstance(results, dict): + results = [results] + + except Exception as e: + results = [] + + with open(json_f, 'r') as fichier: + for ligne in fichier: + # Charger chaque ligne comme un dictionnaire JSON + dictionnaire = json.loads(ligne) + results.append(dictionnaire) + continue + return results def _set_embedding_abstract_file(self): for filename in os.listdir(self.config['retention_dir']): @@ -154,21 +173,7 @@ def _set_embedding_abstract_file(self): if os.path.exists(pth_filename): print(f"{pth_filename} already exists !") continue - try: - results = load_results(json_f) - # fix bug if abstracts is a dict - if isinstance(results, dict): - results = [results] - - except Exception as e: - results = [] - - with open(json_f, 'r') as fichier: - for ligne in fichier: - # Charger chaque ligne comme un dictionnaire JSON - dictionnaire = json.loads(ligne) - results.append(dictionnaire) - continue + results = self._get_data_abstracts_file(json_f) self.mem.save_pth(self.mem.encode_abstracts(results,genname),genname) def manage_abstracts(self): @@ -200,9 +205,48 @@ def get_files_abstracts_embeddings(self): return matching_files - def get_abstracts(self): - results = [] - for filename in os.listdir(self.config['retention_dir']): - if filename.startswith('abstract_') and filename.endswith('.json'): - results.extend(load_results(os.path.join(self.config['retention_dir'], filename))) - return [dict(t) for t in {tuple(d.items()) for d in results}] + def build_dataset_abstracts_annotations(self): + import re,os + + pattern = re.compile("abstracts_\\d+.json") + for root, dirs, files in os.walk(self.config['retention_dir']): + for filename in files: + if pattern.search(filename): + abstracts_json = os.path.join(root, filename) + abstracts_gen = filename.split('.json')[0] + abstracts_scores = self.mem.get_filename_pth(abstracts_gen).split('.pth')[0]+"_scores.json" + print(abstracts_json) + abstracts_data = self._get_data_abstracts_file(abstracts_json) + abstracts_annot = load_results(abstracts_scores) + doi_list = [] + topicalDescriptor_list = [] + pmid_list = [] + reference_id_list = [] + for abstract in abstracts_data: + if 'doi' not in abstract: + continue + doi = abstract['doi'] + if doi in abstracts_annot: + for tag in abstracts_annot[doi]: + topicalDescriptor_list.append(tag) + doi_list.append(doi) + + if 'reference_id' in abstract: + reference_id_list.append(abstract['reference_id']) + else: + reference_id_list.append(None) + if 'pmid' in abstract: + pmid_list.append(abstract['pmid']) + else: + pmid_list.append(None) + + df = pd.DataFrame({ + 'doi': doi_list, + 'topicalDescriptor': topicalDescriptor_list, + 'pmid' : pmid_list, + 'reference_id' : reference_id_list + }) + outf = self.config['retention_dir']+f"/QueryResultEntry_{abstracts_gen}.csv" + print(outf) + df.to_csv(outf, index=False) + diff --git a/llm_semantic_annotator/core.py b/llm_semantic_annotator/core.py index 12169eb..82aa699 100644 --- a/llm_semantic_annotator/core.py +++ b/llm_semantic_annotator/core.py @@ -52,7 +52,6 @@ def main_populate_abstract_embeddings(config_all): config = setup_general_config(config_all,'populate_abstract_embeddings') mem = ModelEmbeddingManager(config_all) - AbstractManager(config,mem).manage_abstracts() def main_compute_tag_chunk_similarities(config_all): @@ -207,4 +206,9 @@ def main_build_graph(config_all): print("RDF graph saved in ",new_f) except json.JSONDecodeError: - print("Erreur de décodage JSON") \ No newline at end of file + print("Erreur de décodage JSON") + +def main_build_dataset_abstracts_annotation(config_all): + config = setup_general_config(config_all,'build_dataset_abstracts_annotation') + mem = ModelEmbeddingManager(config_all) + AbstractManager(config,mem).build_dataset_abstracts_annotations() \ No newline at end of file diff --git a/llm_semantic_annotator/misc/scientific_abstract_rdf_annotator.py b/llm_semantic_annotator/misc/scientific_abstract_rdf_annotator.py index 4f129e7..dfa3fab 100644 --- a/llm_semantic_annotator/misc/scientific_abstract_rdf_annotator.py +++ b/llm_semantic_annotator/misc/scientific_abstract_rdf_annotator.py @@ -1,6 +1,7 @@ from rdflib import Graph, Literal, BNode, Namespace, URIRef from rdflib.namespace import DC, DCTERMS, RDF, RDFS, XSD, PROV, SKOS import datetime +import urllib def create_rdf_graph(results_complete_similarities, encoder_name, @@ -45,7 +46,7 @@ def create_rdf_graph(results_complete_similarities, abstracts_processed = len(results_complete_similarities) for doi, complete_similarities in results_complete_similarities.items(): - doi_uri = URIRef(f"https://doi.org/{doi}") + doi_uri = URIRef(urllib.parse.quote(f"https://doi.org/{doi}")) for tag, similarity in complete_similarities.items(): tag_uri = URIRef(tag) annotation_node = BNode() From 4f7a89a824ff435402d8914f481f8b514da04abc Mon Sep 17 00:00:00 2001 From: Olivier Filangi Date: Tue, 22 Oct 2024 18:51:02 +0200 Subject: [PATCH 4/6] fix dataset forum export --- llm_semantic_annotator/abstract/abstract_manager.py | 7 ++++--- 1 file changed, 4 insertions(+), 3 deletions(-) diff --git a/llm_semantic_annotator/abstract/abstract_manager.py b/llm_semantic_annotator/abstract/abstract_manager.py index 2361785..4bb4d38 100644 --- a/llm_semantic_annotator/abstract/abstract_manager.py +++ b/llm_semantic_annotator/abstract/abstract_manager.py @@ -246,7 +246,8 @@ def build_dataset_abstracts_annotations(self): 'pmid' : pmid_list, 'reference_id' : reference_id_list }) - outf = self.config['retention_dir']+f"/QueryResultEntry_{abstracts_gen}.csv" - print(outf) - df.to_csv(outf, index=False) + if not df.empty: + outf = self.config['retention_dir']+f"/QueryResultEntry_{abstracts_gen}.csv" + print(outf) + df.to_csv(outf, index=False) From 229cea54f16ad5c7d33e857678bd631ad7c1f421 Mon Sep 17 00:00:00 2001 From: Olivier Filangi Date: Wed, 23 Oct 2024 13:41:02 +0200 Subject: [PATCH 5/6] change conf files --- config/all-demo.json | 84 +++++++++++++++++++ config/chmo.json | 32 +++++++ ...ansformon_foodon.json => foodon-demo.json} | 15 +--- .../{mesh_evaluation.json => mesh-demo.json} | 19 ++--- config/mesh_example.json | 44 ---------- config/{1-article.json => ms-demo.json} | 0 config/ncbi-taxon-demo.json | 20 +++++ ...nteom-example.json => planteome-demo.json} | 0 config/simple.json | 4 - config/{igepp.json => transformon-demo.json} | 25 ++---- 10 files changed, 155 insertions(+), 88 deletions(-) create mode 100644 config/all-demo.json create mode 100644 config/chmo.json rename config/{transformon_foodon.json => foodon-demo.json} (60%) rename config/{mesh_evaluation.json => mesh-demo.json} (61%) delete mode 100644 config/mesh_example.json rename config/{1-article.json => ms-demo.json} (100%) create mode 100644 config/ncbi-taxon-demo.json rename config/{planteom-example.json => planteome-demo.json} (100%) rename config/{igepp.json => transformon-demo.json} (73%) diff --git a/config/all-demo.json b/config/all-demo.json new file mode 100644 index 0000000..37c22a0 --- /dev/null +++ b/config/all-demo.json @@ -0,0 +1,84 @@ +{ + "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", + "threshold_similarity_tag_chunk" : 0.60, + "threshold_similarity_tag" : 0.80, + "batch_size" : 32, + + "populate_owl_tag_embeddings" : { + "ontologies": { + "planteome_link" : { + "peco": { + "url": "http://purl.obolibrary.org/obo/peco.owl", + "prefix": "http://purl.obolibrary.org/obo/PECO_", + "format": "xml", + "label" : "", + "properties": [""] + }, + "po": { + "url": "http://purl.obolibrary.org/obo/po.owl", + "prefix": "http://purl.obolibrary.org/obo/PO_", + "format": "xml", + "label" : "", + "properties": [""] + }, + "pso": { + "url": "http://purl.obolibrary.org/obo/pso.owl", + "prefix": "http://purl.obolibrary.org/obo/PSO_", + "format": "xml", + "label" : "", + "properties": [""] + }, + "to": { + "url": "http://purl.obolibrary.org/obo/to.owl", + "prefix": "http://purl.obolibrary.org/obo/TO_", + "format": "xml", + "label" : "", + "properties": [""] + } + }, + "technology_link" : { + "ms": { + "url": "http://purl.obolibrary.org/obo/ms.owl", + "prefix": "http://purl.obolibrary.org/obo/MS_", + "format": "xml", + "label" : "", + "properties": [""] + } + }, + "mesh_link" : { + "mesh": { + "filepath" : "data/mesh/mesh_concept.nt", + "prefix": "http://id.nlm.nih.gov/mesh/", + "format": "nt", + "label" : "", + "properties": [""] + } + }, + "chemical_link" : { + "chmo" : { + "url": "http://purl.obolibrary.org/obo/chmo.owl", + "prefix": "http://purl.obolibrary.org/obo/CHMO_", + "format": "xml", + "label" : "", + "properties": [""] + + } + } + }, + "debug_nb_terms_by_ontology" : -1 + }, + "populate_ncbi_taxon_tag_embeddings" : { + "regex" : "(assic.*)|(arab.*)" , + "tags_per_file" : 2000 + }, + "populate_abstract_embeddings" : { + "abstracts_per_file" : 5, + "from_file" : { + "json_files" : [ + "data/abstracts/abstracts_1.json", + "data/abstracts/abstracts_2.json" + ] + } + + } +} diff --git a/config/chmo.json b/config/chmo.json new file mode 100644 index 0000000..82717c0 --- /dev/null +++ b/config/chmo.json @@ -0,0 +1,32 @@ +{ + "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", + "threshold_similarity_tag_chunk" : 0.60, + "threshold_similarity_tag" : 0.80, + "batch_size" : 32, + + "populate_owl_tag_embeddings" : { + "ontologies": { + "chemical_link" : { + "chmo" : { + "url": "http://purl.obolibrary.org/obo/chmo.owl", + "prefix": "http://purl.obolibrary.org/obo/CHMO_", + "format": "xml", + "label" : "", + "properties": [""] + + } + } + }, + "debug_nb_terms_by_ontology" : -1 + }, + "populate_abstract_embeddings" : { + "abstracts_per_file" : 50, + "from_file" : { + "json_files" : [ + "data/abstracts/abstracts_1.json", + "data/abstracts/abstracts_2.json" + ] + } + + } +} diff --git a/config/transformon_foodon.json b/config/foodon-demo.json similarity index 60% rename from config/transformon_foodon.json rename to config/foodon-demo.json index ca75842..9030f27 100644 --- a/config/transformon_foodon.json +++ b/config/foodon-demo.json @@ -1,20 +1,11 @@ { "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", - "threshold_similarity_tag_chunk" : 0.50, + "threshold_similarity_tag_chunk" : 0.65, "threshold_similarity_tag" : 0.80, "batch_size" : 32, "populate_owl_tag_embeddings" : { "ontologies": { - "transformon_link" : { - "po2": { - "filepath" : "data/ontology/TransformON_V6.0.ttl", - "prefix": "http://opendata.inrae.fr/PO2/Ontology/TransformON/", - "format": "turtle", - "label" : "", - "properties": [""] - } - }, "foodon_link" : { "foodon": { "url": "https://github.com/FoodOntology/foodon/raw/refs/tags/v2024-07-12/foodon.owl", @@ -31,8 +22,10 @@ "abstracts_per_file" : 50, "from_file" : { "json_files" : [ - "data/abstracts/abstracts_food-function-2024-yali-ran.json" + "data/abstracts/abstracts_1.json", + "data/abstracts/abstracts_2.json" ] } + } } diff --git a/config/mesh_evaluation.json b/config/mesh-demo.json similarity index 61% rename from config/mesh_evaluation.json rename to config/mesh-demo.json index 21f74b1..ad572a2 100644 --- a/config/mesh_evaluation.json +++ b/config/mesh-demo.json @@ -1,18 +1,18 @@ { "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", - "threshold_similarity_tag_chunk" : 0.40, + "threshold_similarity_tag_chunk" : 0.60, "threshold_similarity_tag" : 0.80, "batch_size" : 32, "populate_owl_tag_embeddings" : { "ontologies": { "mesh_link" : { - "mesh_descriptor": { - "filepath" : "data/mesh/mesh_descriptor.nt", + "mesh": { + "filepath" : "data/mesh/mesh_concept.nt", "prefix": "http://id.nlm.nih.gov/mesh/", "format": "nt", "label" : "", - "properties": [""] + "properties": [""] } } }, @@ -20,13 +20,10 @@ }, "populate_abstract_embeddings" : { "abstracts_per_file" : 50, - - "from_ncbi_api" : { - "ncbi_api_chunk_size" : 20, - "debug_nb_ncbi_request" : -1, - "retmax" : 20, - "selected_term" : [ - "Crops%2C+Agricultural%2Fmetabolism%5BMeSH%5D" + "from_file" : { + "json_files" : [ + "data/abstracts/abstracts_1.json", + "data/abstracts/abstracts_2.json" ] } } diff --git a/config/mesh_example.json b/config/mesh_example.json deleted file mode 100644 index d6352dc..0000000 --- a/config/mesh_example.json +++ /dev/null @@ -1,44 +0,0 @@ -{ - "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", - "threshold_similarity_tag_chunk" : 0.60, - "threshold_similarity_tag" : 0.80, - "batch_size" : 32, - - "populate_owl_tag_embeddings" : { - "ontologies": { - "mesh_link" : { - "mesh": { - "filepath" : "data/mesh/mesh_concept.nt", - "prefix": "http://id.nlm.nih.gov/mesh/", - "format": "nt", - "label" : "", - "properties": [""] - }, - "mesh_descriptor": { - "filepath" : "data/mesh/mesh_descriptor.nt", - "prefix": "http://id.nlm.nih.gov/mesh/", - "format": "nt", - "label" : "", - "properties": [""] - } - } - }, - "debug_nb_terms_by_ontology" : -1 - }, - "populate_ncbi_taxon_tag_embeddings" : { - "regex" : "uman" , - "tags_per_file" : 2000 - }, - "populate_abstract_embeddings" : { - "abstracts_per_file" : 50, - - "from_ncbi_api" : { - "ncbi_api_chunk_size" : 20, - "debug_nb_ncbi_request" : -1, - "retmax" : 20, - "selected_term" : [ - "Crops%2C+Agricultural%2Fmetabolism%5BMeSH%5D" - ] - } - } -} diff --git a/config/1-article.json b/config/ms-demo.json similarity index 100% rename from config/1-article.json rename to config/ms-demo.json diff --git a/config/ncbi-taxon-demo.json b/config/ncbi-taxon-demo.json new file mode 100644 index 0000000..38dcbaf --- /dev/null +++ b/config/ncbi-taxon-demo.json @@ -0,0 +1,20 @@ +{ + "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", + "threshold_similarity_tag_chunk" : 0.65, + "threshold_similarity_tag" : 0.80, + "batch_size" : 32, + + "populate_ncbi_taxon_tag_embeddings" : { + "regex" : "(assic.*)|(arab.*)" , + "tags_per_file" : 2000 + }, + "populate_abstract_embeddings" : { + "abstracts_per_file" : 50, + "from_file" : { + "json_files" : [ + "data/abstracts/abstracts_1.json", + "data/abstracts/abstracts_2.json" + ] + } + } +} diff --git a/config/planteom-example.json b/config/planteome-demo.json similarity index 100% rename from config/planteom-example.json rename to config/planteome-demo.json diff --git a/config/simple.json b/config/simple.json index 0b86519..0227932 100644 --- a/config/simple.json +++ b/config/simple.json @@ -35,10 +35,6 @@ "json_files" : [ "data/abstracts/abstracts_1.json", "data/abstracts/abstracts_2.json" - ], - "text_files" : [ - "data/abstracts/abstracts_3.txt", - "data/abstracts/abstracts_4.txt" ] } diff --git a/config/igepp.json b/config/transformon-demo.json similarity index 73% rename from config/igepp.json rename to config/transformon-demo.json index dca00c0..261c1ff 100644 --- a/config/igepp.json +++ b/config/transformon-demo.json @@ -1,7 +1,7 @@ { "encodeur" : "sentence-transformers/all-MiniLM-L6-v2", "threshold_similarity_tag_chunk" : 0.65, - "threshold_similarity_tag" : 0.85, + "threshold_similarity_tag" : 0.80, "batch_size" : 32, "populate_owl_tag_embeddings" : { @@ -35,35 +35,24 @@ "label" : "", "properties": [""] } - }, - "technology_link" : { - "ms": { - "url": "http://purl.obolibrary.org/obo/ms.owl", - "prefix": "http://purl.obolibrary.org/obo/MS_", - "format": "xml", - "label" : "", - "properties": [""] - } } }, "debug_nb_terms_by_ontology" : -1 }, - - "populate_gbif_taxon_tag_embeddings" : { + "populate_ncbi_taxon_tag_embeddings" : { + "regex" : "(assic.*)|(arab.*)" , "tags_per_file" : 2000 }, - "populate_abstract_embeddings" : { "abstracts_per_file" : 500, "from_ncbi_api" : { + "ncbi_api_chunk_size" : 200, "debug_nb_ncbi_request" : -1, - "debug_nb_abstracts_by_search" : -1, - "retmax" : 15000, + "retmax" : 2000, "selected_term" : [ - "metabolomics+AND+plant", - "mass+AND+spectrometry+AND+glucosinolate", - "metabolomics+AND+glucosinolate" + "Crops%2C+Agricultural%2Fmetabolism%5BMeSH%5D" ] } + } } From 33d88575ad649efc547864aee9b620012f951dd2 Mon Sep 17 00:00:00 2001 From: Olivier Filangi Date: Wed, 23 Oct 2024 13:41:15 +0200 Subject: [PATCH 6/6] fix --- exec-sbatch-gpu.sh | 14 +-- exec.sh | 102 ++++++++++++------ .../abstract/abstract_manager.py | 80 ++++++++++++-- llm_semantic_annotator/core.py | 77 ++++++------- .../similarity/model_embedding_manager.py | 10 +- .../similarity_evaluator.py | 3 + llm_semantic_annotator/tag/owl_tag_manager.py | 32 +++++- 7 files changed, 215 insertions(+), 103 deletions(-) diff --git a/exec-sbatch-gpu.sh b/exec-sbatch-gpu.sh index f9f559c..bb6cd9a 100755 --- a/exec-sbatch-gpu.sh +++ b/exec-sbatch-gpu.sh @@ -15,15 +15,7 @@ source ./check_slurm_memory.sh . env/bin/activate conffile=config/igepp.json -#export TOKENIZERS_PARALLELISM=false -#rm -rf igepp_w*/ - -check_slurm_memory -python -m llm_semantic_annotator $conffile populate_owl_tag_embeddings -check_slurm_memory -python -m llm_semantic_annotator $conffile populate_gbif_taxon_tag_embeddings -check_slurm_memory -python -m llm_semantic_annotator $conffile populate_abstract_embeddings -check_slurm_memory -python -m llm_semantic_annotator $conffile compute_tag_chunk_similarities + +python -m llm_semantic_annotator $conffile 1 + diff --git a/exec.sh b/exec.sh index e81d868..2ccd132 100755 --- a/exec.sh +++ b/exec.sh @@ -1,11 +1,61 @@ #!/bin/bash -if [ "$#" -ne 1 ]; then - echo "Usage: $0 " +help() { + cat << EOF +Usage: $0 + +Commands: + 1. Pseudo workflow [2,4,5,6,7] + 2. Populate OWL tag embeddings + 3. Populate NCBI Taxon tag embeddings + 4. Populate abstract embeddings + 5. Compute similarities between tags and abstract chunks + 6. Display similarities information + 7. Build turtle knowledge graph + 8. Build dataset abstracts annotations CSV file + 9. Evaluate encoder with MeSH descriptors (experimental) + +Details: + 2: Compute TAG embeddings for all ontologies defined in the populate_owl_tag_embeddings section + 3: Compute TAG embeddings for NCBI Taxon + 4: Compute ABSTRACT embeddings (title + sentences) for all abstracts in the dataset + 5: Compute similarities between TAGS and ABSTRACTS + 6: Display similarities information on the console + 7: Generate turtle file with information {score, tag} for each DOI + 8: Generate CSV file with [doi, tag, pmid, reference_id] + +EOF +} + +# Check for help option +if [[ "$1" == "-h" ]]; then + help + exit 0 +fi + +# Check for correct number of arguments +if [ "$#" -lt 2 ]; then + echo "Error: Not enough arguments." + echo "Usage: $0 [options]" + echo "Use '$0 -h' for more information." + exit 1 +fi + +config_file=$1 +command=$2 + +# Validate config file +if [ ! -f "$config_file" ]; then + echo "Error: Config file '$config_file' does not exist." + exit 1 +fi + +# Validate command is an integer +if ! [[ "$command" =~ ^[0-9]+$ ]]; then + echo "Error: Command must be an integer." exit 1 fi -conffile="$1" venv_name="llm_semantic_annotator_env" # Fonction pour créer l'environnement virtuel s'il n'existe pas @@ -31,44 +81,32 @@ run_command() { execute_command() { case $1 in - 1) run_command python3 -m llm_semantic_annotator "$conffile" populate_owl_tag_embeddings ;; - 2) run_command python3 -m llm_semantic_annotator "$conffile" populate_ncbi_taxon_tag_embeddings ;; - 3) run_command python3 -m llm_semantic_annotator "$conffile" populate_abstract_embeddings ;; - 4) run_command python3 -m llm_semantic_annotator "$conffile" compute_tag_chunk_similarities ;; - 5) run_command python3 -m llm_semantic_annotator "$conffile" display_summary ;; - 6) run_command python3 -m llm_semantic_annotator "$conffile" build_rdf_graph ;; - 7) run_command python3 -m llm_semantic_annotator "$conffile" build_dataset_abstracts_annotations ;; - 8) run_command python3 -m llm_semantic_annotator "$conffile" evaluate_encoder ;; - *) echo "Invalid option" ;; + 2) run_command python3 -m llm_semantic_annotator "$config_file" populate_owl_tag_embeddings ;; + 3) run_command python3 -m llm_semantic_annotator "$config_file" populate_ncbi_taxon_tag_embeddings ;; + 4) run_command python3 -m llm_semantic_annotator "$config_file" populate_abstract_embeddings ;; + 5) run_command python3 -m llm_semantic_annotator "$config_file" compute_tag_chunk_similarities ;; + 6) run_command python3 -m llm_semantic_annotator "$config_file" display_summary ;; + 7) run_command python3 -m llm_semantic_annotator "$config_file" build_rdf_graph ;; + 8) run_command python3 -m llm_semantic_annotator "$config_file" build_dataset_abstracts_annotations ;; + 9) run_command python3 -m llm_semantic_annotator "$config_file" evaluate_encoder ;; + *) echo "Invalid option" ;; esac } # Créer l'environnement virtuel s'il n'existe pas create_venv_if_not_exists -echo "What would you like to execute?" -echo "1. Pseudo workflow [2,4,5,6,7]" -echo "2. populate_owl_tag_embeddings" -echo "3. populate_ncbi_taxon_tag_embeddings" -echo "4. populate_abstract_embeddings" -echo "5. compute similarities between tags and chunks abstracts" -echo "6. display similarities information" -echo "7. build turtle knowledge graph" -echo "8. build dataset abstracts annotations" -echo "9. evaluate encoder with mesh descriptors (experimental)" -read -p "Enter your choice (1-9): " choice - -case $choice in +case $command in 1) - run_command python3 -m llm_semantic_annotator "$conffile" populate_owl_tag_embeddings - #run_command python3 -m llm_semantic_annotator "$conffile" populate_ncbi_taxon_tag_embeddings - run_command python3 -m llm_semantic_annotator "$conffile" populate_abstract_embeddings - run_command python3 -m llm_semantic_annotator "$conffile" compute_tag_chunk_similarities - run_command python3 -m llm_semantic_annotator "$conffile" build_rdf_graph - run_command python3 -m llm_semantic_annotator "$conffile" display_summary + run_command python3 -m llm_semantic_annotator "$config_file" populate_owl_tag_embeddings + #run_command python3 -m llm_semantic_annotator "$config_file" populate_ncbi_taxon_tag_embeddings + run_command python3 -m llm_semantic_annotator "$config_file" populate_abstract_embeddings + run_command python3 -m llm_semantic_annotator "$config_file" compute_tag_chunk_similarities + run_command python3 -m llm_semantic_annotator "$config_file" build_rdf_graph + run_command python3 -m llm_semantic_annotator "$config_file" display_summary ;; 2|3|4|5|6|7|8|9) - execute_command $((choice - 1)) + execute_command $command ;; *) echo "Invalid choice" diff --git a/llm_semantic_annotator/abstract/abstract_manager.py b/llm_semantic_annotator/abstract/abstract_manager.py index 4bb4d38..dd9cbc7 100644 --- a/llm_semantic_annotator/abstract/abstract_manager.py +++ b/llm_semantic_annotator/abstract/abstract_manager.py @@ -5,13 +5,17 @@ import xml.etree.ElementTree as ET from pathlib import Path import pandas as pd - +import rdflib +from collections import defaultdict + class AbstractManager: - def __init__(self, config, model_embedding_manager): + def __init__(self, config,model_embedding_manager,tags_manager): self.config = config self.abstracts_per_file=config.get('abstracts_per_file', 100) self.mem = model_embedding_manager + self.tags_manager = tags_manager + if 'from_ncbi_api' in config: self.retmax = self.config.get('from_ncbi_api').get('retmax',10000) self.debug_nb_req = self.config.get('from_ncbi_api').get('debug_nb_ncbi_request',-1) @@ -205,9 +209,52 @@ def get_files_abstracts_embeddings(self): return matching_files + + def build_ascendants_terms(self,ascendants_dict,graphs): + + for graph in graphs: + g = graph['g'] + prefix = graph['prefix'] + query = """ SELECT ?term ?ascendant WHERE { + ?term rdfs:subClassOf* ?ascendant . + FILTER(STRSTARTS(STR(?term), '"""+ prefix + """')) + FILTER(STRSTARTS(STR(?ascendant), '"""+ prefix + """')) + } """ # Exécuter la requête + + results = g.query(query) # Remplir le dictionnaire avec les résultats + for row in results: + term = str(row.term) + ascendant = str(row.ascendant) + if term != ascendant: # Éviter d'ajouter le terme lui-même comme ascendant + ascendants_dict[term].append(ascendant) # Afficher le dictionnaire + + # we add ascendants of ascendants to avoid future requests + ascendants_dict_to_add = {} + for term in ascendants_dict: + listAscendants = ascendants_dict[term] + liste_asc = listAscendants.copy() + + while liste_asc: + ascendant = liste_asc.pop(0) + if ascendant not in ascendants_dict: + ascendants_dict_to_add[ascendant] = liste_asc.copy() + + ascendants_dict.update(ascendants_dict_to_add) + + print("update dictionnary size :",len(ascendants_dict)) + return ascendants_dict + + def build_dataset_abstracts_annotations(self): import re,os - + import time + graphs = self.tags_manager.get_graphs_ontologies() + ascendants_dict = defaultdict(list) + debut = time.time() + self.build_ascendants_terms(ascendants_dict,graphs) + duree = time.time() - debut + print(f"loading terms with ancestors : {duree:.4f} secondes") + pattern = re.compile("abstracts_\\d+.json") for root, dirs, files in os.walk(self.config['retention_dir']): for filename in files: @@ -228,18 +275,29 @@ def build_dataset_abstracts_annotations(self): doi = abstract['doi'] if doi in abstracts_annot: for tag in abstracts_annot[doi]: - topicalDescriptor_list.append(tag) - doi_list.append(doi) - if 'reference_id' in abstract: - reference_id_list.append(abstract['reference_id']) + reference_id=abstract['reference_id'] else: - reference_id_list.append(None) + reference_id=None + if 'pmid' in abstract: - pmid_list.append(abstract['pmid']) + pmid=abstract['pmid'] else: - pmid_list.append(None) - + pmid=None + + # the tag is the term + topicalDescriptor_list.append(tag) + doi_list.append(doi) + reference_id_list.append(reference_id) + pmid_list.append(pmid) + + # ancestors + for ancestor in ascendants_dict[tag]: + topicalDescriptor_list.append(ancestor) + doi_list.append(doi) + reference_id_list.append(reference_id) + pmid_list.append(pmid) + df = pd.DataFrame({ 'doi': doi_list, 'topicalDescriptor': topicalDescriptor_list, diff --git a/llm_semantic_annotator/core.py b/llm_semantic_annotator/core.py index 82aa699..c9cde66 100644 --- a/llm_semantic_annotator/core.py +++ b/llm_semantic_annotator/core.py @@ -24,63 +24,57 @@ def setup_general_config(config_all,methode): return config -def main_populate_owl_tag_embeddings(config_all): - """Fonction principale pour générer et stocker les embeddings de tags dans une base.""" +def get_owl_tag_manager(config_all): config = setup_general_config(config_all,'populate_owl_tag_embeddings') - - # Utilisez les paramètres de config ici - print(f"Ontologies : {config['ontologies']}") - print(f"Nb terms to compute : {config['debug_nb_terms_by_ontology']}") - mem = ModelEmbeddingManager(config_all) - - OwlTagManager(config,mem).manage_tags() + return OwlTagManager(config,mem) -def main_populate_gbif_taxon_tag_embeddings(config_all): +def get_gbif_taxon_tag_manager(config_all): config = setup_general_config(config_all,'populate_gbif_taxon_tag_embeddings') mem = ModelEmbeddingManager(config_all) + return TaxonTagManager(config,mem) - TaxonTagManager(config,mem).manage_gbif_taxon_tags() - -def main_populate_ncbi_taxon_tag_embeddings(config_all): +def get_ncbi_taxon_tag_manager(config_all): config = setup_general_config(config_all,'populate_ncbi_taxon_tag_embeddings') mem = ModelEmbeddingManager(config_all) + return TaxonTagManager(config,mem) - TaxonTagManager(config,mem).manage_ncbi_taxon_tags() - -def main_populate_abstract_embeddings(config_all): - +def get_abstract_manager(config_all): config = setup_general_config(config_all,'populate_abstract_embeddings') mem = ModelEmbeddingManager(config_all) - AbstractManager(config,mem).manage_abstracts() + return AbstractManager(config,mem,get_owl_tag_manager(config_all)) + +def main_populate_owl_tag_embeddings(config_all): + """Fonction principale pour générer et stocker les embeddings de tags dans une base.""" + get_owl_tag_manager(config_all).manage_tags() + +def main_populate_gbif_taxon_tag_embeddings(config_all): + get_gbif_taxon_tag_manager(config_all).manage_gbif_taxon_tags() + +def main_populate_ncbi_taxon_tag_embeddings(config_all): + get_ncbi_taxon_tag_manager(config_all).manage_ncbi_taxon_tags() + +def main_populate_abstract_embeddings(config_all): + get_abstract_manager(config_all).manage_abstracts() def main_compute_tag_chunk_similarities(config_all): """Fonction principale pour calculer la similarité entre tous les tags et chunks.""" - config_owl = setup_general_config(config_all,'populate_owl_tag_embeddings') - config_abstract = setup_general_config(config_all,'populate_abstract_embeddings') - - mem = ModelEmbeddingManager(config_all) - - - tags_pth_files = OwlTagManager(config_owl,mem).get_files_tags_embeddings() + tags_pth_files = get_owl_tag_manager(config_all).get_files_tags_embeddings() if len(tags_pth_files) == 0: raise FileNotFoundError("No tags embeddings found") - tags_taxon_pth_files = TaxonTagManager(config_owl,mem).get_files_tags_ncbi_taxon_embeddings() - - if len(tags_taxon_pth_files) == 0: - warnings.warn("No tags taxon embeddings found") - + tags_taxon_pth_files = get_ncbi_taxon_tag_manager(config_all).get_files_tags_ncbi_taxon_embeddings() tags_pth_files.extend(tags_taxon_pth_files) - abstracts_pth_files = AbstractManager(config_abstract,mem).get_files_abstracts_embeddings() + abstracts_pth_files = get_abstract_manager(config_all).get_files_abstracts_embeddings() if len(abstracts_pth_files) == 0: raise FileNotFoundError("No abstracts embeddings found") ### Loading tags embeddings ### ----------------------- + mem = ModelEmbeddingManager(config_all) tag_embeddings_all = {} tag_embeddings = {} @@ -132,26 +126,21 @@ def get_scores_files(retention_dir): return scores_files def get_results_complete_similarities_and_tags_embedding(config_all): + mem = ModelEmbeddingManager(config_all) + scores_files = [] retention_dir = config_all['retention_dir'] - mem = ModelEmbeddingManager(config_all) - config_owl = setup_general_config(config_all,'populate_owl_tag_embeddings') - config_abstract = setup_general_config(config_all,'populate_abstract_embeddings') scores_files = get_scores_files(retention_dir) - - tags_pth_files = OwlTagManager(config_owl,mem).get_files_tags_embeddings() + tags_pth_files = get_owl_tag_manager(config_all).get_files_tags_embeddings() if len(tags_pth_files) == 0: raise FileNotFoundError("No tags embeddings found") - tags_taxon_pth_files = TaxonTagManager(config_owl,mem).get_files_tags_ncbi_taxon_embeddings() - - if len(tags_taxon_pth_files) == 0: - warnings.warn("No tags taxon embeddings found") - + tags_taxon_pth_files = get_ncbi_taxon_tag_manager(config_all).get_files_tags_ncbi_taxon_embeddings() tags_pth_files.extend(tags_taxon_pth_files) - abstracts_pth_files = AbstractManager(config_abstract,mem).get_files_abstracts_embeddings() + + abstracts_pth_files = get_abstract_manager(config_all).get_files_abstracts_embeddings() if len(abstracts_pth_files) == 0: raise FileNotFoundError("No abstracts embeddings found") @@ -209,6 +198,4 @@ def main_build_graph(config_all): print("Erreur de décodage JSON") def main_build_dataset_abstracts_annotation(config_all): - config = setup_general_config(config_all,'build_dataset_abstracts_annotation') - mem = ModelEmbeddingManager(config_all) - AbstractManager(config,mem).build_dataset_abstracts_annotations() \ No newline at end of file + get_abstract_manager(config_all).build_dataset_abstracts_annotations() \ No newline at end of file diff --git a/llm_semantic_annotator/similarity/model_embedding_manager.py b/llm_semantic_annotator/similarity/model_embedding_manager.py index 9af645f..9009798 100644 --- a/llm_semantic_annotator/similarity/model_embedding_manager.py +++ b/llm_semantic_annotator/similarity/model_embedding_manager.py @@ -48,7 +48,15 @@ # https://huggingface.co/spaces/mteb/leaderboard # mixedbread-ai/mxbai-embed-large-v1 -class ModelEmbeddingManager: +class Singleton(type): + _instances = {} + def __call__(cls, *args, **kwargs): + if cls not in cls._instances: + cls._instances[cls] = super().__call__(*args, **kwargs) + return cls._instances[cls] + + +class ModelEmbeddingManager(metaclass=Singleton): def __init__(self,config): self.config=config self.retention_dir = config['retention_dir'] diff --git a/llm_semantic_annotator/similarity_evaluator.py b/llm_semantic_annotator/similarity_evaluator.py index 4358ad6..96c3da2 100644 --- a/llm_semantic_annotator/similarity_evaluator.py +++ b/llm_semantic_annotator/similarity_evaluator.py @@ -22,6 +22,9 @@ def evaluate_abstracts(results_score_abstracts, abstracts): for abstract in abstracts: doi = abstract['doi'] + if 'descriptor' not in abstract: + continue + actual_terms = abstract['descriptor'] if doi in results_score_abstracts: predicted_terms = [ str(desc).split("/").pop() for desc in results_score_abstracts[doi].keys() ] diff --git a/llm_semantic_annotator/tag/owl_tag_manager.py b/llm_semantic_annotator/tag/owl_tag_manager.py index 559f1ca..c9b5482 100644 --- a/llm_semantic_annotator/tag/owl_tag_manager.py +++ b/llm_semantic_annotator/tag/owl_tag_manager.py @@ -31,13 +31,15 @@ def get_corpus(self,ontology_group_name,ontologies): for ontology in self.get_ontologies(ontologies): self.build_corpus(ontology, ontology_group_name,ontologies[ontology],self.debug_nb_terms_by_ontology) - + def _get_local_filepath_ontology(self,ontology,format): + return self.retention_dir+"/"+ontology+"."+format + # Charger le fichier OWL local def get_ontologies(self,list_ontologies): for ontology,values in list_ontologies.items(): - filepath = self.retention_dir+"/"+ontology+"."+values['format'] + filepath = self._get_local_filepath_ontology(ontology,values['format']) # utilisation d'un fichier local if 'filepath' in values: @@ -183,4 +185,28 @@ def get_tags(self): if filename.startswith('tag_') and filename.endswith('.json'): results.append(load_results(os.path.join(self.retention_dir, filename))) # Remove duplicates - return [dict(t) for t in {tuple(d.items()) for d in results}] \ No newline at end of file + return [dict(t) for t in {tuple(d.items()) for d in results}] + + def get_graphs_ontologies(self): + graphs = [] + + for link_name,ontologies in self.ontologies_by_link.items(): + for ontology,values in ontologies.items(): + g = Graph() + if 'filepath' in values: + g.parse(values['filepath'], format=values['format']) + else: + filepath = self._get_local_filepath_ontology(ontology,values['format']) + if not os.path.exists(filepath): + raise FileNotFoundError(f"Le fichier '{filepath}' n'existe pas.") + + g.parse(filepath, format=values['format']) + + graphs.append({ + 'g' : g, + 'link_name' : link_name, + 'prefix' : values['prefix'], + 'properties' : values['properties'], + 'label' : values['label'] + }) + return graphs \ No newline at end of file