gebhart/patrepeval huggingface dataset:
Unc45b Forms a Cytosolic Complex with Hsp90 and Targets the Unfolded Myosin Motor Domain (2008)

Myosin folding and assembly in striated muscle is mediated by the general chaperones Hsc70 and Hsp90 and a myosin specific co-chaperone, UNC45. Two UNC45 genes are found in vertebrates, including a striated muscle specific form, Unc45b. We have investigated the role of Unc45b in myosin folding. Epitope tagged murine Unc45b (Unc45b(Flag)) was expressed in muscle and non-muscle cells and bacteria, isolated and characterized. The protein is a soluble monomer in solution with a compact folded rod-shaped structure of approximately 19 nm length by electron microscopy. When over-expressed in striated muscle cells, Unc45b(Flag) fractionates as a cytosolic protein and isolates as a stable complex with Hsp90. Purified Unc45b(Flag) re-binds Hsp90 and forms a stable complex in solution. The endogenous Unc45b in muscle cell lysates is also found associated with Hsp90. The Unc45b(Flag)/Hsp90 complex binds the partially folded myosin motor domain when incubated with myosin subfragments synthesized in a reticulocyte lysate. This binding is independent of the myosin rod or light chains. Unc45b(Flag) does not bind native myosin subfragments consistent with a chaperone function. More importantly, Unc45b(Flag) enhances myosin motor domain folding during de novo motor domain synthesis indicating that it has a direct role in myosin maturation. Thus, mammalian Unc45b is a cytosolic protein that forms a stable complex with Hsp90, selectively binds the unfolded conformation of the myosin motor domain, and promotes motor domain folding.
HB-EGF Is a Potent Inducer of Tumor Growth and Angiogenesis (2004)

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to stimulate the growth of a variety of cells in an autocrine or paracrine manner. Although HB-EGF is widely expressed in tumors compared with normal tissue, its contribution to tumorigenicity is unknown. HB-EGF can be produced as a membrane-anchored form (pro-HB-EGF) and later processed to a soluble form (s-HB-EGF), although a significant amount of pro-HB-EGF remains uncleaved on the cell surface. To understand the roles of two forms of HB-EGF in promoting tumor growth, we have studied the effects of HB-EGF expression in the process of tumorigenesis using in vitro and in vivo systems. We demonstrate here that in EJ human bladder cancer cells containing a tetracycline-regulatable s-HB-EGF or pro-HB-EGF expression system, s-HB-EGF expression increased their transformed phenotypes, including growth rate, colony-forming ability, and activation of cyclin D1 promoter, as well as induction of vascular endothelial growth factor in vitro. Moreover, s-HB-EGF or wild-type HB-EGF induced the expression and activities of the metalloproteases, MMP-9 and MMP-3, leading to enhanced cell migration. In vivo studies also demonstrated that tumor cells expressing s-HB-EGF or wild-type HB-EGF significantly enhanced tumorigenic potential in athymic nude mice and exerted an angiogenic effect, increasing the density and size of tumor blood vessels. However, cells expressing solely pro-HB-EGF did not exhibit any significant tumorigenic potential. These findings establish s-HB-EGF as a potent inducer of tumor growth and angiogenesis and suggest that therapeutic intervention aimed at the inhibition of s-HB-EGF functions may be useful in cancer treatment.
Genetic Basis of IgE Responsiveness: Relevance to the Atopic Diseases (1995)

Genetic analysis of 170 subjects in 11 extended Amish families revealed evidence for linkage of five markers in chromosome 5q31.1 with a gene controlling total serum IgE levels. No linkage was found between these markers and specific IgE antibody levels. Analysis of total IgE within a subset of 128 IgE-antibody-negative sib pairs confirmed evidence for linkage to 5q31.1, especially IL4 (p = 4 x 10(-6)). These and other data suggest that IL4 or a nearby gene regulates IgE production in a non-antigen-specific (noncognate) fashion and provide evidence for a possible link between asthma and the IL4 gene.
A SEROEPIDEMIOLOGIC STUDY OF ADENOVIRUS-ASSOCIATED VIRUS INFECTION IN INFANTS AND CHILDREN (1971)

Journal Article A SEROEPIDEMIOLOGIC STUDY OF ADENOVIRUS-ASSOCIATED VIRUS INFECTION IN INFANTS AND CHILDREN Get access NEIL R. BLACKLOW, NEIL R. BLACKLOW 1Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. DAVID HOGGAN, M. DAVID HOGGAN 2Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar MITZI S. SERENO, MITZI S. SERENO 1Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar CARL D. BRANDT, CARL D. BRANDT 3Virology Section, Research Foundation of Children's Hospital of the District of Columbia and Department of Pediatrics, George Washington University School of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar HYUN WHA KIM, HYUN WHA KIM 3Virology Section, Research Foundation of Children's Hospital of the District of Columbia and Department of Pediatrics, George Washington University School of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar ROBERT H. PARROTT, ROBERT H. PARROTT 3Virology Section, Research Foundation of Children's Hospital of the District of Columbia and Department of Pediatrics, George Washington University School of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar ROBERT M. CHANOCK ROBERT M. CHANOCK 1Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 94, Issue 4, October 1971, Pages 359–366, https://doi.org/10.1093/oxfordjournals.aje.a121331 Published: 01 October 1971 Article history Received: 29 March 1971 Published: 01 October 1971
Oral Administration of Collagen Conjugated with Cholera Toxin Induces Tolerance to Type II Collagen and Suppresses Chondritis in an Animal Model of Autoimmune Ear Disease (2001)

B10.RIII (H-2r) mice were orally administered cyanogen bromide peptide 11 (CB11) or cholera toxin B (CTB)-conjugated CB11 to induce tolerance in collagen-induced autoimmune ear disease. Oral administration of a high dosage of CB11 provided partial protection from chondritis. However, administration of a tiny amount of CTB-CB11 conjugate effectively suppressed chondritis. Oral administration of CTB-CB11 conjugate did not alter the stimulation of T cells in vitro or the fine specificities of B cells. The oral administration of CTB-CB11 caused a higher level of type II collagen-specific IgG and its subclass. Interestingly, increases of TH1 cytokine (interferon-gamma) in Peyer's patches and of TH1/TH2 cytokines (interleukin-2 and interleukin-4) in lymph nodes were detected in mice that had been fed CTB-CB11. An increase of CD8+ T cells in the Peyer's patches with a decrease of CD8+ T cells in lymph nodes was seen in mice that had been fed CTB-CB11. These results suggest that protection from chondritis by oral administration of minute amounts of CTB-CB11 conjugate can be achieved by a mechanism distinct from that of conventional oral tolerance induction.
Rising CO 2 Levels and the Fecundity of Forest Trees (2001)

We determined the reproductive response of 19-year-old loblolly pine (Pinus taeda) to 4 years of carbon dioxide (CO2) enrichment (ambient concentration plus 200 microliters per liter) in an intact forest. After 3 years of CO2 fumigation, trees were twice as likely to be reproductively mature and produced three times as many cones and seeds as trees at ambient CO2 concentration. A disproportionate carbon allocation to reproduction under CO2 enrichment results in trees reaching maturity sooner and at a smaller size. This reproductive response to future increases in atmospheric CO2 concentration is expected to change loblolly dispersal and recruitment patterns.
Spontaneous and cytokine-evoked production of matrix metalloproteinases by bone marrow and peripheral blood pre-B cells in childhood acute lymphoblastic leukaemia. (2005)

The present work focused on the study of the secretory activity of pre-B acute lymphoblastic leukaemia (ALL) cells harvested from bone marrow (BM) and peripheral blood (PB) in 16 children. The basal and cytokine (SDF-1, GM-CSF, bFGF, VEGF)-stimulated secretions of gelatinases 2 and 9 (MMPs-2 and -9) and expression of their genes were monitored by zymography and RT-PCR, respectively. A wide heterogeneity was found in the secretory capacities of these cells. The basal secretion of MMP-9 was more frequently observed than that of MMP-2 in both cell types. The cytokines VEGF and bFGF were found to induce predominant stimulatory effects on the MMP-2 secretion. In contrast, GM-CSF was shown to exert a more pronounced activation of the MMP-9 production. Experiments using inhibitors of metabolic pathways (U0126, LY294002 and SN50) revealed that the secretion of MMP-9 was mediated through PI3/MEK1 kinases. The MMP-2 secretion appeared to be however, stimulated through a different metabolic pathway. The microfluorimetric approach showed that the basal and stimulated secretions of MMPs-2 and -9 depended on the extracellular calcium pool. The cytokines VEGF and bFGF represent potent factors increasing the intracellular calcium concentration with similar kinetics. In contrast, GM-CSF was found to activate a verapamil-sensitive efflux of indo-1 from cytosol suggesting that this cytokine could be responsible for the activation of xenobiotic membrane transporters. Experiments using the trypan blue exclusion test demonstrated that bFGF, in contrast to VEGF and GM-CSF, markedly augmented pre-B ALL cell survival. Further investigations into a possible correlation between the plasma concentrations of MMP-2 and -9, VEGF, bFGF and GM-CSF, and the poor evolution of pre-B ALL in children could have valuable diagnostic implications.
Apolipoprotein CIII Links Hyperlipidemia With Vascular Endothelial Cell Dysfunction (2008)

Our results suggest that apoCIII is a crucial link between dyslipidemia and insulin resistance in vascular endothelial cells with consequential deleterious effects on their atheroprotective functions.
Nitric oxide signaling specificity — the heart of the problem (2002)

Nitric oxide (NO) is a gaseous free radical that functions as an endogenous mediator in numerous tissues. Because NO is both reactive and highly diffusible, its formation must be tightly regulated to control its synthesis and to specify its signaling. Indeed, molecular studies of the NO synthase (NOS) family of enzymes have elaborated a variety of mechanisms, including protein interactions, lipid modifications and protein phosphorylation cascades that spatially and temporally control NO biosynthesis. These mechanisms determine both the upstream cellular signals that stimulate NO formation and the downstream molecular targets for NO. Understanding these cellular pathways that control NOS will help us to elucidate the functional roles of NO and provide novel strategies to treat diseases associated with NO abnormalities.
Reactions of phosphorus compounds. XIII. Preparations and reactions of cyclopropyltriphenylphosphonium bromide (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactions of phosphorus compounds. XIII. Preparations and reactions of cyclopropyltriphenylphosphonium bromideEdward Ernest Schweizer, Carl J. Berninger, and John Guthrie ThompsonCite this: J. Org. Chem. 1968, 33, 1, 336–339Publication Date (Print):January 1, 1968Publication History Published online1 May 2002Published inissue 1 January 1968https://pubs.acs.org/doi/10.1021/jo01265a068https://doi.org/10.1021/jo01265a068research-articleACS PublicationsRequest reuse permissionsArticle Views497Altmetric-Citations51LEARN 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
Role of C9orf140 in the promotion of colorectal cancer progression and mechanisms of its upregulation via activation of STAT5, β-catenin and EZH2 (2014)

C9orf140 is a newly identified and characterized gene which is associated with cell proliferation and tumorigenicity. Expression of C9orf140 is upregulated in human gastric cancer and colorectal cancer (CRC); however, little is known about its role in CRC progression. We have investigated the clinical significance, biological effects and mechanisms of C9orf140 signaling. We found that the expression of C9orf140 is dramatically increased in a subset of CRC and correlates significantly with vascular invasion and lymph node metastasis. Our finding showed that knockdown of C9orf140 significantly reduced cell proliferation and invasion in vitro and dramatically increased overall survival and decreased lung metastasis in vivo. Conversely, overexpression of C9orf140 significantly increased lung metastasis and shortened overall survival when compared with control tumors. C9orf140-induced CRC cell invasion may depend on promoting the epithelial-mesenchymal transition progression. STAT5 may directly interact with the enhancer of zeste homolog 2 (EZH2) and β-catenin to enhance C9orf140 gene transactivation. Furthermore, C9orf140 may participate in cell invasion which is induced by STAT5, EZH2 or β-catenin activation. We describe the role of C9orf140 in CRC progression and find that C9orf140 overexpression may be regulated by STAT5, EZH2 and β-catenin interaction.
Production and Characterization of Monoclonal Antibody to Botulinum Neurotoxin Type B Light Chain by Phage Display (2008)

A monoclonal antibody to the light chain of botulinum neurotoxin type B (BoNT/B) was generated and its protective activity was evaluated in vivo. A chimeric rabbit/human Fab library was generated using bone marrow and spleen cDNAs of rabbits immunized with the BoNT/B light chain, and three monoclonal antibodies specific to the catalytic domain of BoNT/B were isolated. One of these clones, BCXRH1, was specific to a conformation-dependent epitope, and partially neutralized the BoNT/B complex in vivo.
Meeting central (2004)

The Meeting Central prototype is a suite of collaboration tools designed to support distributed meetings. The tools' minimalist design provides only those features that have the most impact on distributed meeting effectiveness. The collaboration suite is built on top of a distributed, extensible, and scalable framework.
Solid support synthesis of ollgothymidylates using phosphorochloridates and 1-alkylimidazoles (1975)

A study of the synthesis of oligothymidylates via phosphotriester intermediates on a polystyrene support is described. The sequence involves condensation of a phenyl nucleoside-3' -phosphorochloridate with the 5'-hydroxyl group of the carrier bound oligonucleotide derivative in the presence of 1-methylimidazole. Conditions for preparation of the phenyl nucleo-side phosphorochloridate as well as for the condensation on the support are discussed. d-TpTpTpT was obtained in 31% overall yield from carrier bound thymidine in one series of experiments, and d-TpTpTpTpT was obtained in 9% yield in another. The cycle for addition of one nucleotide unit can be completed in about six hours.
The antiangiogenic agent SU5416 down-regulates phorbol ester-mediated induction of cyclooxygenase 2 expression by inhibiting nicotinamide adenine dinucleotide phosphate oxidase activity. (2003)

Increased expression of cyclooxygenase (COX) 2 and the production of PGs appear to provide a survival advantage to transformed cells through the inhibition of apoptosis, increased attachment to extracellular matrix, increased invasiveness and the stimulation of angiogenesis. The purpose of this study was to determine whether an angiogenic antagonist, SU5416, could inhibit endogenous and phorbol 12-myristate 13-acetate (PMA)-mediated induction of COX-2 expression. SU5416 (5 micro M) inhibited endogenous as well as PMA-mediated induction of COX-2 expression when analyzed by immunoblot and Northern blot analysis. However, COX-1 expression remained unchanged under similar conditions. PMA is a potent inducer of reactive oxygen species that can play an important role during the induction of COX-2 expression. Our results demonstrated that PMA-mediated induction of COX-2 expression was found to be dependent on NADPH oxidase activity. An inhibitor of NADPH oxidase (diphenyleneiodonium chloride) blocked the PMA-mediated induction of COX-2 expression. The oxidase complex exhibited a temporal pattern of activation after exposure to PMA in which maximum activation was observed at 30 min after the addition of PMA. Activation of NADPH oxidase was also inhibited by SU5416, whereas an inhibitor of epidermal growth factor receptor signaling was unable to prevent the PMA-mediated induction of NADPH oxidase activity. When we blocked the PMA-mediated production of reactive oxygen species by blocking NADPH oxidase with SU5416, COX-2 expression and PGE(2) synthesis were also inhibited. Our results suggest that inhibition of NADPH oxidase activity, blocking of COX-2 expression, and PGE(2) synthesis may represent novel targets for SU5416.
The pH-dependent rate of action of local anesthetics on the node of Ranvier. (1977)

Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility.
Location of the dipteran specificity region in a lepidopteran-dipteran crystal protein from Bacillus thuringiensis (1990)

Two highly related crystal protein genes from Bacillus thuringiensis subsp. kurstaki HD-1, designated cryIIA and cryIIB (previously named cryB1 and cryB2, respectively), were used to study host range specificity. Their respective gene products are 87% identical but exhibit different toxicity spectra; CryIIA is toxic to both mosquito and tobacco hornworm larvae, whereas CryIIB is toxic only to the latter. Hybrids of the cryIIA and cryIIB genes were generated, and their resultant gene products were assayed for toxicity. A short segment of CryIIA corresponding to residues 307 through 382 was shown to be sufficient for altering host range specificity-i.e., when this region replaced the corresponding segment of CryIIB, the resulting hybrid protein acquired toxicity against mosquitoes. The CryIIA and CryIIB polypeptides differ by only 18 amino acids in this region, indicating that very few amino acid changes can have a substantial effect on the toxicity spectra of these proteins.
Modelling genetic and clinical heterogeneity in epithelial ovarian cancers (2011)

The biology underlying early-stage epithelial ovarian cancer (EOC) development is poorly understood. Identifying biomarkers associated with early-stage disease could have a significant impact on reducing mortality. Here, we describe establishment of a three-dimensional (3D) in vitro genetic model of EOC initiation and early-stage neoplastic progression. Normal primary ovarian epithelial (POE) cells, immortalized using hTERT (immortalised ovarian epithelial [IOE] cells), were partially transformed by overexpressing the CMYC oncogene (IOE(CMYC) cells). Subsequent expression of mutant alleles of KRAS (KRAS(G12V)) or BRAF (BRAF(V600E)) created double-mutant lines (IOE(CMYC.KRAS) and IOE(CMYC.BRAF)). The transformed phenotype of IOE(CMYC) cells was further enhanced in concert with KRAS(G12V)/BRAF(V600E) expression, as in vitro analyses indicated that IOE(CMYC) cells had undergone morphological and phenotypic changes characteristic of neoplastic progression. When cultured as 3D spheroids, IOE cells underwent growth arrest, reminiscent of nonproliferative, unstimulated POE in vivo. In contrast, IOSE(CMYC+BRAF/KRAS) cells formed highly proliferative, poly-aggregate spheroid structures, showing increased expression of the Wilms tumour 1 tumourigenic marker and MIB1 proliferation marker. Transcriptomic analyses identified different gene expression profiles between the different cell lines and novel candidate genes (e.g. RGS4, CTGF and THBS1) that are somatically altered in EOCs. Gene expression signatures were compared with signatures from primary EOCs; tumours with IOE(CMYC) 'like' signatures were more likely to be high grade (P = 0.018); tumours with BRAF signatures were associated with improved relapse-free survival (P = 0.003). In conclusion, we have established in vitro 3D models of early-stage EOCs, which reflect genetic and phenotypic heterogeneity of the disease. Molecular genetic characteristics of these models correlated with molecular and clinical features of primary EOCs.