gebhart/patrepeval huggingface dataset:
Extracellular Release of the Atheroprotective Heat Shock Protein 27 Is Mediated by Estrogen and Competitively Inhibits acLDL Binding to Scavenger Receptor-A (2008)

We recently identified heat shock protein 27 (HSP27) as an estrogen receptor beta (ERbeta)-associated protein and noted its role as a biomarker for atherosclerosis. The current study tests the hypothesis that HSP27 is protective against the development of atherosclerosis. HSP27 overexpressing (HSP27o/e) mice were crossed to apoE-/- mice that develop atherosclerosis when fed a high-fat diet. Aortic en face analysis demonstrated a 35% reduction (P < or =0.001) in atherosclerotic lesion area in apoE-/-HSP27o/e mice compared to apoE-/- mice, but primarily in females. Serum -HSP27levels were 10-fold higher in female apoE-/-HSP27o/e mice compared to males, and there was a remarkable inverse correlation between circulating HSP27 levels and lesion area in both male and female mice (r(2)=0.78, P < or =0.001). Mechanistic in vitro studies showed upregulated HSP27 expression and secretion in macrophages treated with estrogen or acLDL. Moreover, exogenous HSP27 added to culture media inhibited macrophage acLDL uptake and competed for the scavenger receptor A (SR-A)--an effect that was abolished with the SR-A competitive ligand fucoidan and absent in macrophages from SR-A-/- mice. Furthermore, extracellular HSP27 decreased acLDL-induced release of the proinflammatory cytokine IL-1beta and increased the release of the antiinflammatory cytokine IL-10. HSP27 is atheroprotective, perhaps because of its ability to compete for the uptake of atherogenic lipids or attenuate inflammation.
Comprehensive molecular characterization of urothelial bladder carcinoma (2014)

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium (2006)

Successful embryo development requires an extensive endometrial angiogenesis in proximity of implantation site. The glycoprotein hCG is produced even before implantation by trophoblast in normal pregnancy. In this manuscript, we demonstrate an angiogenic effect of hCG in several in vivo (chick chorioallantoïc membrane, matrigel plug assay, aortic ring assay) and in vitro experimental models. In contrast, human placental lactogen (hPL) did not display angiogenic properties. LH/hCG receptor was detected in endothelial cells by reverse-transcriptase polymerase chain reaction (RT-PCR) and by Western blotting. In mice aortic ring assay, angiostimulation by hCG was abrogated by deletion of LH/hCG receptor (LuRKO mice). Use of recombinant hCG and anti-hCG antibody (Ab) further confirmed the specificity of this angiogenic activity. By using dibutyryl cAMP, adenylate cyclase, or protein kinase A inhibitors, we demonstrate that hCG-mediated angiogenesis involves adenylyl-cyclase-protein kinase A activation. Addition of hCG to endometrial epithelial epithelial cells, but not to cultured endothelial cells, stimulated vascular endothelial growth factor (VEGF). VEGF and hCG also displayed additive activities. Altogether, these data demonstrate that peritrophoblastic angiostimulation may result from a paracrine dialogue between trophoblast, epithelial, and endothelial cells through hCG and VEGF.
MOLECULAR AND STRUCTURAL BIOLOGY OF THYROID HORMONE RECEPTORS (1998)

1. Thyroid hormone receptors (TR) are expressed from two separate genes (alpha and beta) and belong to the nuclear receptor superfamily, which also contains receptors for steroids, vitamins and prostaglandins. 2. Unliganded TR are bound to DNA thyroid hormone response elements (TRE) predominantly as homodimers, or as heterodimers with retinoid X-receptors (RXR), and are associated with a complex of proteins containing corepressor proteins. Ligand binding promotes corepressor dissociation and binding of a coactivator. 3. Recent studies from our group have focused on the acquisition and use of X-ray crystallographic structures of ligand-binding domains (LBD) of both the rat (r) TR alpha and the human (h) TR beta bound to several different ligands. We have also developed ligands that bind selectively to the TR beta, which may provide ways to explore the differential functions of TR alpha compared with TR beta isoforms. 4. The LBD is comprised mostly of alpha-helices. The ligand is completely buried in the receptor and forms part of its hydrophobic core. Kinetic studies suggest that the limiting step in formation of high-affinity ligand-receptor complexes is the rate of folding of the receptor around the ligand. Ligands can be fitted tightly in the ligand-binding pocket and small differences in this fitting may explain many structure-activity relationships. Interestingly, analysis of the structures of antagonists suggests that they have chemical groups, 'extensions', that could impair receptor folding around them and, thus, prevent the agonist-induced conformation changes in the receptor. 5. The TR structures allowed us to see that the mutations that occur in the syndrome of generalized resistance to thyroid hormone are located in the vicinity of the ligand-binding pocket. 6. X-ray structure of the TR has also been used to guide construction of mutations in the TR surface that block binding of various proteins important for receptor function. Studies with these TR mutants reveal that the interfaces for homo- and heterodimerization map to similar residues in helix 10 and 11 and also allow the definition of the surface for binding of coactivators, which appears to be general for nuclear receptors. Formation of this surface, which involves packing of helix 12 of the TR into a scaffold formed by helices 3 and 5, appears to be the major change in the receptor structure induced by hormone occupancy.
The effect of bacteriophages T4 and HAP1 on in vitro melanoma migration (2009)

We believe that these observations are of importance for any further attempts to use bacteriophage preparations in antibacterial treatment. The risk of antibiotic-resistant hospital infections strongly affects cancer patients and these results suggest the possibility of beneficial phage treatment. We also believe that they will contribute to the general understanding of bacteriophage biology, as bacteriophages, extremely ubiquitous entities, are in permanent contact with human organisms.
Aspergillusand aspergillosis (1992)

Aspergillus and aspergillosis Get access J.C. Rhodes, J.C. Rhodes Search for other works by this author on: Oxford Academic PubMed Google Scholar H.E. Jensen, H.E. Jensen Search for other works by this author on: Oxford Academic PubMed Google Scholar A.M. Nilius, A.M. Nilius Search for other works by this author on: Oxford Academic PubMed Google Scholar C.R. Chitambar, C.R. Chitambar Search for other works by this author on: Oxford Academic PubMed Google Scholar S.G. Farmer, S.G. Farmer Search for other works by this author on: Oxford Academic PubMed Google Scholar R.G. Washburn, R.G. Washburn Search for other works by this author on: Oxford Academic PubMed Google Scholar P.E. Steele, P.E. Steele Search for other works by this author on: Oxford Academic PubMed Google Scholar T.W. Amlung T.W. Amlung Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Medical and Veterinary Mycology, Volume 30, Issue Supplement_1, January 1992, Pages 51–57, https://doi.org/10.1080/02681219280000761 Published: 01 January 1992
A 160-kD Systemin Receptor on the Surface of Lycopersicon peruvianum Suspension-Cultured Cells (1999)

Systemin, an 18-amino acid polypeptide wound signal, activates defense genes in leaves of young tomato plants and induces rapid alkalinization of media containing suspension-cultured Lycopersicon peruvianum cells. A monoiodinated form of a systemin analog synthesized with Tyr-2 and Ala-15 (Tyr-2,Ala-15-systemin) likewise exhibits similar biological activities. (125)I-Tyr-2,Ala-15-systemin rapidly, reversibly, and saturably bound to suspension-cultured L. peruvianum cells with a K(d) of 0.17 nM and a Hill coefficient of 0. 92. The specificity of binding was assessed with alanine-substituted systemin analogs and was found to correlate with their respective biological activities. Treatment of suspension-cultured cells with methyl jasmonate increased the total binding of (125)I-Tyr-2, Ala-15-systemin more than threefold, suggesting that methyl jasmonate was activating transcription of the gene encoding the binding protein. Treatment of cells with cycloheximide markedly decreased binding of iodinated systemin to the cells, indicating that the binding protein was constantly being synthesized and degraded. A photoaffinity systemin analog, N-(4-[p-azidosalicylamido]butyl)-3'(2'-Cys-3, Ala-15-systemindithiol)propionamide, specifically labeled a 160-kD cell surface protein, and the labeling was completely inhibited by a 20-fold excess of unlabeled systemin. These data indicate that a 160-kD protein may be the physiological receptor for systemin in suspension-cultured cells.
Isolation of polymorphic DNA segments from human chromosome 21 (1985)

A somatic cell hybrid line containing only human chromosome 21 on a mouse background has been used as the source of DNA for construction of a recombinant phage library. Individual phages containing human inserts have been identified. Repeat-free human DNA subclones have been prepared and used to screen for restriction fragment length polymorphisms to provide genetic markers on chromosome 21. Nine independently isolated clones used as probes identified a total of 11 new RFLPs. Four of the DNA probes recovered from the library have been mapped unequivocally to chromosome 21 using a panel of somatic cell hybrid lines. A fifth probe detected an RFLP on chromosome 21 as well as sequences on other chromosomes. This set of RFLPs may now form the basis for construction of a genetic linkage map of human chromosome 21.
Structure and Evolution of Neurexophilin (1996)

Using affinity chromatography on immobilized alpha-latrotoxin, we have purified a novel 29 kDa protein, neurexophilin, in a complex with neurexin l alpha. Cloning revealed that rat and bovine neurexophilins are composed of N-terminal signal peptides, nonconserved N-terminal domains (20% identity over 80 residues), and highly homologous C-terminal sequences (85% identity over 169 residues). Analysis of genomic clones from mice identified two distinct neurexophilin genes, one of which is more homologous to rat neurexophilin and the other to bovine neurexophilin. The first neurexophilin gene is expressed abundantly in adult rat and mouse brain, whereas no mRNA corresponding to the second gene was detected in rodents despite its abundant expression in bovine brain, suggesting that rodents and cattle primarily express distinct neurexophilin genes. RNA blots and in situ hybridizations revealed that neurexophilin is expressed in adult rat brain at high levels only in a scattered subpopulation of neurons that probably represent inhibitory interneurons; by contrast, neurexins are expressed in all neurons. Neurexophilin contains a signal sequence and is N-glycosylated at multiple sites, suggesting that it is secreted and binds to the extracellular domain of neurexin l alpha. This hypothesis was confirmed by binding recombinant neurexophilin to the extracellular domains of neurexin l alpha. Together our data suggest that neurexophilin constitutes a secreted glycoprotein that is synthesized in a subclass of neurons and may be a ligand for neurexins.
Heparanase Induces Vascular Endothelial Growth Factor Expression: Correlation with p38 Phosphorylation Levels and Src Activation (2006)

Heparanase is an endo-beta-D-glucuronidase involved in cleavage of heparan sulfate moieties and hence participates in extracellular matrix (ECM) degradation and remodeling. Traditionally, heparanase activity was correlated with the metastatic potential of a variety of tumor-derived cell types. Cloning of the heparanase gene indicated that heparanase expression is up-regulated in a variety of primary human tumors. In some cases, heparanase up-regulation correlated with increased tumor vascularity, an angiogenic feature that could be recapitulated in a number of in vitro and in vivo models. The mechanism by which heparanase enhances angiogenic responses is not entirely clear but is thought to be mediated primarily by release of ECM-resident angiogenic growth factors such as basic fibroblast growth factor and vascular endothelial growth factor (VEGF). Here, we examined the possibility that heparanase directly participates in VEGF gene regulation. We provide evidence that heparanase overexpression in human embryonic kidney 293, MDA-MB-435 human breast carcinoma, and rat C6 glioma cells resulted in a 3- to 6-fold increase in VEGF protein and mRNA levels, which correlated with elevation of p38 phosphorylation. Moreover, heparanase down-regulation in B16 mouse melanoma cells by a specific siRNA vector was accompanied by a decrease in VEGF and p38 phosphorylation levels, suggesting that VEGF gene expression is regulated by endogenous heparanase. Interestingly, a specific p38 inhibitor did not attenuate VEGF up-regulation by heparanase whereas Src inhibitors completely abrogated this effect. These results indicate, for the first time, that heparanase is actively involved in the regulation of VEGF gene expression, mediated by activation of Src family members.
Experimental Study of Temperature Distributions and Thermal Transport During Radiofrequency Current Therapy of the Intervertebral Disc (1996)

The authors concluded that the mechanism of observed clinical improvement from radiofrequency heating of intervertebral discs is not thermal denervation of the disc and that the physicochemical state of the disc is important to consider when designing a therapeutic heating protocol if thermal denervation is clinically desired.
Parametric Study of Sweeping Jet Actuators for Separation Control (2010)

In this paper, studies of separation control over a generic Multiple Flap Airfoil (MFA) using sweeping jet actuator arrays are presented. These jets, exiting from millimeter-scale nozzles, oscillate from side-to-side in a sweeping manner similar to windshield wipers and are henceforth referred to as sweeping jet actuators. Different flap sizes and flap deflections up to 45 o were investigated in the experiments. The MFA, with integrated rows of sweeping jet actuators at several chordwise locations on the flaps, enabled an extensive variation of geometrical and fluid dynamical parameters to study separation control. The effect of flap size, actuator location and actuation parameters on the lift and drag coefficients of the airfoil are discussed.
PYRIMIDINES. V. DEHALOGENATION AND NUCLEAR REDUCTION OF CERTAIN PYRIMIDINES1 (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPYRIMIDINES. V. DEHALOGENATION AND NUCLEAR REDUCTION OF CERTAIN PYRIMIDINES1VICTOR H. SMITH and B. E. CHRISTENSENCite this: J. Org. Chem. 1955, 20, 7, 829–838Publication Date (Print):July 1, 1955Publication History Published online1 May 2002Published inissue 1 July 1955https://pubs.acs.org/doi/10.1021/jo01125a004https://doi.org/10.1021/jo01125a004research-articleACS PublicationsRequest reuse permissionsArticle Views1422Altmetric-Citations41LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Time-resolved fluorescence tomography in cancer research: backward versus toward geometry (2009)

Fluorescence Diffuse Optical Tomography is an optical non-invasive molecular technique for cancer imaging. Depending on the accessibility of the organ two main geometries might be considered, reflection or transmission. We will present first experimental and reconstruction comparison between these two geometries, on a laboratory time resolved bench. Both acquisitions were made using a fluorophore inclusion positioned in a liquid phantom, with breast comparable optical properties. We successfully reconstructed all fluorophore positions examined in both geometries. Reflection geometry suffers of many drawbacks that we have to deal with. We will present all challenges it implies, and also what are the advantages to use time resolved techniques in both geometries.
Site-specific mutagenesis by O6-alkylguanines located in the chromosomes of mammalian cells: influence of the mammalian O6-alkylguanine-DNA alkyltransferase. (1989)

A plasmid was constructed in which a single guanine residue was replaced with either O6-methylguanine or O6-ethylguanine, two of the DNA adducts formed by carcinogenic alkylating agents. The vectors were introduced in parallel into a pair of Chinese hamster ovary cells, in which one member of the pair was deficient in the repair enzyme O6-alkylguanine-DNA alkyltransferase (mex-) and the other was proficient in this activity (mex+). The vectors integrated into and replicated within the respective host genomes. After intrachromosomal replication, the DNA sequence in the vicinity of the originally adducted site of each integrated vector was amplified from the host genome by using the polymerase chain reaction and was analyzed for mutations. High levels of mutation were observed from the O6-methylguanine- and O6-ethylguanine-containing vectors replicated in mex- cells (approximately 19% for O6-methylguanine and approximately 11% for O6-ethylguanine). DNA sequencing revealed the induced mutations to be almost exclusively G----A transitions. By contrast, little or no mutagenesis was detected when the adducted vectors were introduced into mex+ cells, indicating the significant role of the O6-alkylguanine-DNA alkyltransferase in the repair of O6-methylguanine and O6-ethylguanine in these mammalian cells.
Optical Alignment and Patterning of Nanoscale Microdomains in a Block Copolymer Thin Film (2006)

Optical 3D alignment of nanocylinders has been successfully attained for thin films of a block copolymer (see figure) comprising azobenzene-containing liquid-crystalline polymers and poly(ethylene oxide) via photoinduced massive migration. The out-of-plane and in-plane alignments are achieved by controlling the film thickness and selection of linear polarization direction upon illumination, respectively.
Heat-Killed Listeria monocytogenes as an Adjuvant Converts Established Murine Th2-Dominated Immune Responses into Th1-Dominated Responses (1998)

We investigated the capacity of heat-killed Listeria monocytogenes (HKL), a potent stimulator of the innate immune system, as a vaccine adjuvant to modify both primary and secondary Ag-specific immune responses. Mice immunized with the Ag keyhole limpet hemocyanin (KLH) mixed with HKL generated a KLH-specific primary response characterized by production of Th1 cytokines and large quantities of KLH-specific IgG2a Ab. Moreover, administration of KLH with HKL as an adjuvant reversed established immune responses dominated by the production of Th2 cytokines and high levels of KLH-specific IgE and induced a Th1-type response with high levels of IFN-gamma and IgG2a and low levels of IgE and IL-4. Neutralization of IL-12 activity at the time of HKL administration blocked the enhancement of IFN-gamma and reduction of IL-4 production, indicating that IL-12, induced by HKL, was responsible for the adjuvant effects on cytokine production. These results suggest that HKL as an adjuvant during immunization can successfully bias the development of Ag-specific cytokine synthesis toward Th1 cytokine production even in the setting of an ongoing Th2-dominated response. Thus, HKL may be clinically effective in vaccine therapies for diseases such as allergy and asthma, which require the conversion of Th2-dominated immune responses into Th1-dominated responses.
Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. (1988)

Camptothecin, a plant alkaloid with antitumor activity, has been shown to be a potent inhibitor of nucleic acid synthesis and a strong inducer of DNA strand breaks in mammalian cells. Previous studies have shown that camptothecin inhibits purified mammalian DNA topoisomerase I by trapping a reversible enzyme-DNA "cleavable complex" (Hsiang et al., J. Biol. Chem., 260: 14873-14878, 1985). Our present studies, using L1210 cells and SV40-infected monkey cells, have shown that camptothecin-induced strand breaks are protein linked. The linked protein is most likely DNA topoisomerase I as revealed by immunoblot analysis, using antibodies against purified mammalian DNA topoisomerase I. Brief heating of camptothecin-treated cells to 65 degrees C resulted in a rapid reduction of the number of protein-linked DNA breaks. Reversal of the camptothecin-induced topoisomerase I-DNA complex by heat was also observed in an in vitro system by using purified mammalian DNA topoisomerase I. Our results suggest that camptothecin interferes with DNA topoisomerase I both in cultured mammalian cells and in the purified system by trapping a reversible enzyme-DNA cleavable complex.