julilili42/papers huggingface dataset:
Methyltransferase genes in Streptomyces rishiriensis: new coumermycin derivatives from gene-inactivation experiments b bThe GenBank accession number for the sequence reported in this paper is AF235050.
2002-10-01

The coumarin antibiotic coumermycin A(1) contains at least eight methyl groups, presumably derived from S-adenosylmethionine. Two putative methyltransferase genes, couO and couP, of the coumermycin A(1) biosynthetic gene cluster were inactivated by in-frame deletion. In the resulting mutants, coumermycin A(1) production was abolished. New coumermycin derivatives were accumulated instead, and were identified by HPLC-MS using selected reaction monitoring via electrospray ionization. couO mutants accumulated a coumermycin derivative lacking the methyl groups at C-8 of the characteristic aminocoumarin rings, whereas in the couP mutant a coumermycin derivative lacking the methyl groups at the 4-hydroxyl groups of the two deoxysugar moieties was identified. These results provided evidence that couO encodes a C-methyltransferase responsible for the transfer of a methyl group to C-8 of the aminocoumarin ring, and couP an O-methyltransferase for methylation of 4-OH of the sugar in the biosynthesis of coumermycin A(1), respectively. C-methylation of the aminocoumarin ring is considered as an early step of coumermycin biosynthesis. Nevertheless, the intermediates with the non-methylated aminocoumarin ring were accepted by the enzymes catalysing the subsequent steps of the pathway. The new, demethylated secondary metabolites were produced in an amount at least as high as that of coumermycin A(1) in the wild-type.
Cytokine concentrations in the amniotic fluid during parturition at term: correlation to lower uterine segment values and to labor
2002-10-01

Background. In previous studies a significant increase in interleukin (IL)‐6 and IL‐8 concentrations in the lower uterine segment parallel to cervical dilatation at term could be found, however only a weak correlation to duration of labor was detected. This study compares amniotic fluid concentrations of interleukin (IL)‐6 and IL‐8 with those in the lower uterine segment, and the duration of labor. Methods. Amniotic fluid and lower uterine segment specimens were obtained from 29 patients during cesarean section at term. The patients were divided into groups according to cervical dilatation (&lt; 2 cm, 2–3.9 cm, 4–6 cm, &gt; 6 cm) and to labor (0 h, &gt; 0–12 h, &gt; 12 h). Interleukin‐6 and IL‐8 concentrations were determined by enzyme immunoassay. Results. Amniotic fluid IL‐6 already increased at 2–3.9 cm ( p = 0.02), while the steepest increase in IL‐8 was observed at &gt; 6 cm ( p = 0.003). No correlation with lower uterine segment values was observed for either of the cytokines. However, the amniotic fluid IL‐6 concentration correlated with labor ( p = 0.0008). Conclusion. The increase in the concentration of IL‐6 in the amniotic fluid earlier than its increase in the lower uterine segment supports the hypothesis that IL‐6 plays a crucial role for the promotion of labor in the first place, and afterwards for the biochemical degradation processes in the lower uterine segment. The fact that the greatest increase in IL‐8 concentration occurs only at &gt; 6 cm indicates that this chemotactic cytokine has only minor significance in the initiation of parturition by its concentration in the amniotic fluid.
Hirschsprung, RET-SOX and beyond: The challenge of examining non-mendelian traits (Review)
2002-10-01

Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a common hereditary disorder causing intestinal obstruction, thereby showing considerable phenotypic variation in conjunction with complex inheritance. Moreover, phenotypic assessment of the disease has been complicated since a subset of the observed mutations is also associated with several additional syndromic anomalies. Coding sequence mutations in e.g. RET, GDNF, EDNRB, EDN3, and SOX10 lead to long-segment (L-HSCR) as well as syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). Furthermore, mutations in the RET gene are responsible for approximately half of the familial and some sporadic cases, strongly suggesting, on the one hand, the importance of non-coding variations and, on the other hand, that additional genes involved in the development of the enteric nervous system still await their discovery. For almost all of the identified HSCR genes incomplete penetrance of the HSCR phenotype has been reported, probably due to modifier loci. Therefore, HSCR has become a model for a complex oligo-/polygenic disorder in which the relationship between different genes creating a non-mendelian inheritance pattern still remains to be elucidated.
Human Serum Adiponectin Levels are not Under Short-Term Negative Control by Free Fatty Acidsin Vivo
2002-10-01

Plasma levels of free fatty acids (FFAs) are elevated when adipose tissue expands and adipocytes become refractory to inhibition of lipolysis by insulin. FFAs have been known for years to have multiple effects on peripheral tissues such as glucose uptake and glycogen synthesis inhibition in skeletal muscle, hepatic gluconeogenesis stimulation, and insulin clearance impairment, altogether favoring whole body insulin resistance, hyperinsulinemia, hyperglycemia, and finally type 2 diabetes mellitus. Besides these metabolic effects, FFAs seem to be able to regulate adipocytokine gene expression. FFAs were shown to repress the expression of the recently discovered adipocyte hormone resistin in an insulin-resistant rat model [1]. In in vitro differentiated adipocytes, FFAs also downregulated the expression of leptin, the most important central regulator of energy expenditure and food intake known to date [2]. This effect of FFAs on gene expression might be mediated by direct activation of specific fatty acid-regulated transcription factors (for review, see [3]).
Right-Sided Cervical Aortic Arch with Stenosis - Treatment with an Extraanatomic Bypass Graft
2002-10-01

Right-sided cervical aortic arch is a very rare vascular anomaly that may lead to stenosis development. Anatomic repair may be impeded by its high course or by abnormal branching of the supraaortic vessels, or both. This report will describe the treatment of a stenotic right-sided cervical aortic arch using an extra-anatomic bypass graft without extracorporeal support in an 11-year-old girl.
The Stereoenantiomers of a Pinacidil Analog Open or Close Cloned ATP-sensitive K+ Channels
2002-10-01

ATP-dependent K(+) channels (K(ATP) channels) are composed of pore-forming subunits Kir6.x and sulfonylurea receptors (SURs). Cyanoguanidines such as pinacidil and P1075 bind to SUR and enhance MgATP binding to and hydrolysis by SUR, thereby opening K(ATP) channels. In the vasculature, openers of K(ATP) channels produce vasorelaxation. Some novel cyanoguanidines, however, selectively reverse opener-induced vasorelaxation, suggesting that they might be K(ATP) channel blockers. Here we have analyzed the interaction of the enantiomers of a racemic cyanoguanidine blocker, PNU-94750, with Kir6.2/SUR channels. In patch clamp experiments, the R-enantiomer (PNU-96293) inhibited Kir6.2/SUR2 channels (IC(50) approximately 50 nm in the whole cell configuration), whereas the S-enantiomer (PNU-96179) was a weak opener. Radioligand binding studies showed that the R-enantiomer was more potent and that it was negatively allosterically coupled to MgATP binding, whereas the S-enantiomer was weaker and positively coupled. Binding experiments also suggested that both enantiomers bound to the P1075 site of SUR. This is the first report to show that the enantiomers of a K(ATP) channel modulator affect channel activity and coupling to MgATP binding in opposite directions and that these opposite effects are apparently mediated by binding to the same (opener) site of SUR.
Business Cycle Volatility in Germany
2002-10-01

Stylized facts suggest that output volatility in OECD countries has declined in recent years. However, the causes and the nature of this decline have so far been analyzed mainly for the United States. In this paper, we analyze whether structural breaks in the dynamics and the volatility of the real output process in Germany can be detected. We report evidence that output volatility has declined in Germany. Yet, this decline in output volatility is not as clear-cut as it is in the case of the United States. In consequence, it is difficult to answer the question whether the decline in output volatility in Germany reflects good economic and monetary policy or merely ?good luck?.
Mg2+ sensitizes KATP channels to inhibition by DIDS: dependence on the sulphonylurea receptor subunit
2002-10-01

ATP-sensitive potassium channels (KATP channels) consist of pore-forming Kir6.x subunits and of sulphonylurea receptors (SURs). In the absence of Mg2+, the stilbene disulphonate, DIDS, irreversibly inhibits KATP channels by binding to the Kir subunit. Here, the effects of Mg2+ on the interaction of DIDS with recombinant KATP channels were studied in electrophysiological and [3H]-glibenclamide binding experiments. In inside-out macropatches, Mg2+ (0.7 mM) increased the sensitivity of KATP channels towards DIDS up to 70 fold (IC50=2.7 μM for Kir6.2/SUR2B). Inhibition of current at DIDS concentrations 10 μM was irreversible. Mg2+ sensitized the truncated Kir6.2Δ26 channel towards inhibition by DIDS only upon coexpression with a SUR subunit (SUR2B). The effect of Mg2+ did not require the presence of nucleotides. [3H]-glibenclamide binding to SUR2B(Y1206S), a mutant with improved affinity for glibenclamide, was inhibited by DIDS. The potency of inhibition was increased by Mg2+ and by coexpression with Kir6.2. In the presence of Mg2+, DIDS inhibited binding of [3H]-glibenclamide to Kir6.2/SUR2B(Y1206S) with IC50=7.9 μM by a non-competitive mechanism. Inhibition was fully reversible. It is concluded that the binding site of DIDS on SUR that is sensed by glibenclamide does not mediate channel inhibition. Instead, Mg2+ binding to SUR may allosterically increase the accessibility and/or reactivity of the DIDS site on Kir6.2. The fact that the Mg2+ effect does not require the presence of nucleotides underlines the importance of this ion in modulating the properties of the KATP channel. British Journal of Pharmacology (2002) 137, 429–440. doi:10.1038/sj.bjp.0704905
The role of the MDR1 gene in the development of multidrug resistance in human hepatoblastoma
2002-10-03

Abstract BACKGROUND The P‐glyprotein (P‐gp), which is a membrane channel encoded by the MDR1 gene, represents a possible explanation for multidrug resistance in human hepatoblastoma (HB). P‐gp shows up‐regulation in tumor cells after chemotherapy; however, to date, its exact role in HB has not been described. The authors investigated the role of the MDR1 gene in the clinical course of patients with HB and in an in vivo model of HB. They also studied the effects of the MDR1 antagonizer PSC 833 on chemotherapy in mice xenotransplanted with HB. METHODS Resected tumor specimens, including both primary tumors and recurrent tumors, from a child suffering from HB were investigated histologically. Cell suspensions from the originally removed tumor were incorporated subcutaneously into nude mice. Animals were treated with cisplatin (CDDP) plus PSC 833. MDR1 gene expression levels in the different resected tumors from the patient and in the xenotransplants after treatment were determined with polymerase chain reaction analysis. RESULTS MDR1 gene expression was increased in the patient's tumors after every course of chemotherapy from 30% to &gt; 190%. In the xenotransplants, MDR1 gene expression was enhanced significantly after chemotherapy ( P CDDP = 0.008; P CDDP+PSC = 0.002). Tumor volumes ( P &lt; 0.001) and serum α‐fetoprotein levels ( P = 0.0002) were significantly lower in the animals that were treated with CDDP + PSC compared with the animals that were treated with CDDP alone. CONCLUSIONS The current results suggest that MDR1 gene expression and P‐gp are a potential mechanism of drug resistance in HB. The chemosensitizer PSC 833 significantly improved the effects of chemotherapy in animals xenotransplanted with HB. These data encourage further studies concerning the role of chemosensitizers in overcoming multidrug resistance in patients with HB. Cancer 2002;95:1795–801. © 2002 American Cancer Society. DOI 10.1002/cncr.10858
Ground state of finite nuclei evaluated from realistic interactions
2002-10-03

Ground state properties of finite nuclei ( O and Ca) are\\nevaluated from realistic nucleon-nucleon interactions. The calculations are\\nbased on the Brueckner-Hartree-Fock approximation. Special attention is paid to\\nthe role of the energy spectrum for the particle states, in particular for\\nthose close to the Fermi energy. Additional binding energy is obtained from the\\ninclusion of the hole-hole scattering term within the framework of the Green\\nfunction approach. Results for the energy distribution of the single-particle\\nstrength and the sensitivity to the nucleon-nucleon interaction are\\ninvestigated. For that purpose three modern nucleon-nucleon interactions are\\nemployed: the Argonne V18, the charge dependent Bonn potential and a realistic\\nnucleon-nucleon interaction which is based on chiral perturbation theory and\\nwhich has recently been fitted by the Idaho group.\\n
Solubility-Normalized Combined Adsorption-Partitioning Sorption Isotherms for Organic Pollutants
2002-10-04

Equilibrium sorption isotherms were measured for five different low-polarity organic compounds (benzene, trichloroethene, 1,2- and 1,4-dichlorobenzene, and phenanthrene) over a wide concentration range. The investigated sorbents can be grouped into the following three classes: (1) humic soil organic matter, which shows linear sorption isotherms (solely partitioning, as observed in the peat sample); (2) carbon materials, which were thermally altered (due to their natural history or industrial production) and thus contain a high specific surface area and exhibit nonlinear isotherms, and (3) pure engineered microporous materials (e.g., zeolites and activated carbon), where adsorption is solely due to a pore-filling process. Sorption of all compounds was fitted very well by the Polanyi-Dubinin-Manes (PDM) model, which for sorbents containing humic organic matter (e.g., peat) was combined with linear partitioning. Both the partitioning and the Polanyi-Dubinin-Manes model predict unique sorption isotherms of similar compounds if the solubility-normalized aqueous concentration is used. In addition, an inverse linear relationship between the distribution coefficient (Kd) and water solubility, which was very well confirmed by the data, is obtained. This also leads to unit-equivalent Freundlich sorption isotherms and explains the often observed apparent correlation between sorption capacity at a given concentration (e.g., Freundlich coefficient) and sorption nonlinearity (Freundlich exponent).
Defective Associations between Blood Vessels and Brain Parenchyma Lead to Cerebral Hemorrhage in Mice Lacking αv Integrins
2002-10-07

Mouse embryos genetically null for the alphav integrin subunit develop intracerebral hemorrhages at midgestation and die shortly after birth. A key question is whether the hemorrhage arises from primary defects in vascular endothelial cells or pericytes or from other causes. We have previously reported normal initiation of cerebral vessels comprising branched tubes of endothelial cells. Here we show that the onset of hemorrhage is not due to defects in pericyte recruitment. Additionally, most alphav-null vessels display ultrastructurally normal endothelium-pericyte associations and normal interendothelial cell junctions. Thus, endothelial cells and pericytes appear to establish their normal relationships in cerebral microvessels. However, by both light and electron microscopy, we detected defective associations between cerebral microvessels and the surrounding brain parenchyma, composed of neuroepithelial cells, glia, and neuronal precursors. These data suggest a novel role for alphav integrins in the association between cerebral microvessels and central nervous system parenchymal cells.
Comparative patterns of postcranial ontogeny in therian Mammals: An analysis of relative timing of ossification events
2002-10-09

Abstract Data on the relative sequence of ossification of postcranial elements for eight therian mammals ( Myotis lucifugus, Homo sapiens, Rattus norvegicus, Mus musculus, Mesocricetus auratus, Cavia porcellus, Didelphis albiventris , and Sminthopsis macroura ) and three outgroups ( Chelydra serpentina, Alligator mississippiensis , and Lacerta vivipara ) were taken from the literature. For each species, a matrix was constructed in which the relative timing of the onset of ossification in 24 elements was summarized. This resulted in 276 event pairs (characters) for each species. Thirty‐three (33.3)% of the characters examined are uniform across all taxa, 16.3% are variable but uninformative in the phylogeny, and 50.4% potentially deliver diagnostic features for clades of two or more taxa. In all species examined, the clavicle is the first bone to appear. Placentalia is not unequivocally diagnosed by the state of any event pair, while Marsupialia has the largest amount of autapomorphies with 18. The acceleration in the timing of ossification of the scapula in relation to the hindlimb in marsupials is most probably causally correlated to movements after birth and during early phases of pre‐weaning life. Marsupials are almost unique among amniotes in that the earliest onset of ossification of at least one element among carpals and among tarsals is simultaneous. Three parsimony analyses, each one with a different reptilian taxon as outgroup, were performed using event pairs as characters. In all cases, results were incongruent with the phylogeny of the studied taxa. J. Exp. Zool. (Mol. Dev. Evol.) 294:264–273, 2002 . © 2002 Wiley‐Liss, Inc.
Quark zero modes in intersecting center vortex gauge fields
2002-10-11

The zero modes of the Dirac operator in the background of center vortex gauge\\nfield configurations in and are examined. If the net flux in D=2\\nis larger than 1 we obtain normalizable zero modes which are mainly localized\\nat the vortices. In D=4 quasi-normalizable zero modes exist for intersecting\\nflat vortex sheets with the Pontryagin index equal to 2. These zero modes are\\nmainly localized at the vortex intersection points, which carry a topological\\ncharge of . To circumvent the problem of normalizability the\\nspace-time manifold is chosen to be the (compact) torus and ,\\nrespectively. According to the index theorem there are normalizable zero modes\\non if the net flux is non-zero. These zero modes are localized at the\\nvortices. On zero modes exist for a non-vanishing Pontryagin index. As\\nin these zero modes are localized at the vortex intersection points.\\n
Cutting Edge: Down-Regulation of MICA on Human Tumors by Proteolytic Shedding
2002-10-15

Abstract The immunoreceptor NKG2D stimulates tumor immunity through activation of CD8 T cells and NK cells. Its ligand MICA has been shown to be broadly expressed on human tumors of epithelial origin. MICA expression correlates with an enrichment of Vδ1 T cells in tumor tissue. We report that human tumor cells spontaneously release a soluble form of MICA encompassing the three extracellular domains, which is present at high levels in sera of patients with gastrointestinal malignancies, but not in healthy donors. Release of MICA from tumor cells is blocked by inhibition of metalloproteinases, concomitantly causing accumulation of MICA on the cell surface. Shedding of MICA by tumor cells may modulate NKG2D-mediated tumor immune surveillance. In addition, determination of soluble MICA levels may be implemented as an immunological diagnostic marker in patients with epithelial malignancies.
Integrated functional genomics approach for the design of patient-individual antitumor vaccines.
2002-10-15

Our aim is to identify as many candidates as possible for tumor-associated T-cell epitopes in individual patients. First, we performed expression profiling of tumor and normal tissue to identify genes exclusively expressed or overexpressed in the tumor sample. Then, using mass spectrometry, we characterized up to 77 different MHC ligands from the same tumor sample. Several of the MHC ligands were derived from overexpressed gene products, one was derived from a proto-oncogene, and another was derived from a frameshift mutation. At least one was identified as an actual T-cell epitope. Thus, we could show that by combining these two analytic tools, it is possible to propose several candidates for peptide-based immunotherapy. We envision the use of this novel integrated functional genomics approach for the design of antitumor vaccines tailored to suit the needs of each patient.
Overexpression of glutamine synthetase is associated with beta-catenin-mutations in mouse liver tumors during promotion of hepatocarcinogenesis by phenobarbital.
2002-10-15

Phenobarbital (PB) is an antiepileptic drug that promotes hepatocarcinogenesis in rodents when administered subsequent to an initiating carcinogen like N-nitrosodiethylamine (DEN). In the mouse, the promotional effect of PB on liver tumor development results from a selective stimulation of clonal outgrowth of hepatocytes harboring activating mutations in the beta-catenin gene. Because glutamine synthetase (GS) has recently been shown to be a putative transcriptional target of beta-catenin, expression of GS during PB-mediated promotion of mouse hepatocarcinogenesis was investigated. Preneoplastic and neoplastic liver lesions were induced in 6-week-old male mice by a single injection of 90 micro g/g body weight of DEN, and groups of mice were subsequently kept on PB-containing (0.05%) or control diet for 39 weeks. In PB-treated mice, 46 of 51 lesions ( approximately 90%) were GS-positive in contrast to only 16 of 46 ( approximately 35%) in mice not treated with PB. Approximately 33% of liver was occupied by neoplastic tissue in PB-treated mice, of which >80% was GS positive. By contrast, only approximately 3.5% of liver consisted of neoplastic tissue in mice treated with DEN only, and approximately 25% of this was GS positive. We have previously shown that beta-catenin mutations are present in approximately 80% of liver tumors from PB-treated mice but are absent in liver tumors from mice treated with DEN only. By analyzing a panel of larger liver tumors, we now observed that tumors harboring beta-catenin mutations were GS positive, whereas tumors without beta-catenin mutations were GS negative. Similarly, tumors from an additional mouse carcinogenicity experiment where PB inhibited rather than promoted hepatocarcinogenesis were mostly GS negative. These data suggest that promotion of hepatocarcinogenesis by PB confers beta-catenin-mutated tumor cells with a selective advantage by up-regulation of GS expression.