7,786 research outputs found

    Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene

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    G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression

    Writing a History of Women's Writing from 700 to 1500

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    How can a history of British women’s writing be written? Such a project must necessarily be collaborative if it is to attempt to be comprehensive, but even then any claim to comprehensiveness has to be qualified: paradoxically the more expansive the history, the more partial it will be. The challenges of writing such a history are perhaps even greater for scholars working in the early periods because we are forced to confront and to rethink many deeply ingrained assumptions about women’s writing. This introductory essay focuses on a period of literary history that is often marginalized in accounts of women’s writing in English: the Middle Ages. It is a widely accepted view that there are only two women writers in English in the period before 1500, and therefore there is little to be said for an age (or ages) when women writers were so much an exception. Furthermore, the two medieval English women writers whose names are widely known, Julian of Norwich (1342/3-after 1416) and Margery Kempe (c.1373-after 1439), did not think of themselves as writers or authors. Nor were they responsible for literature as it is thought of today—they did not compose poetry, or romances, or fiction of any sort. Even these two ‘named’ women writers do not comfortably fit established evolutionary models of women’s literary history over the longue durée, with their emphases on the spread of literacy, the bias towards print culture, and the emergence of the woman poet, and ultimately of the professional author of drama or fiction. Yet the difficulty of locating how the medieval period fits in to literary history is not unique to women’s writing: medieval understandings of authorship, literature, and national identity, and the contexts and processes of writing and textual circulation were quite distinct from later periods and therefore deemed problematic more generally. This essay explores some of these issues and reflects on the difficulties we face writing a history of early women's writing

    Writing a History of Women's Writing from 700 to 1500

    No full text
    How can a history of British women’s writing be written? Such a project must necessarily be collaborative if it is to attempt to be comprehensive, but even then any claim to comprehensiveness has to be qualified: paradoxically the more expansive the history, the more partial it will be. The challenges of writing such a history are perhaps even greater for scholars working in the early periods because we are forced to confront and to rethink many deeply ingrained assumptions about women’s writing. This introductory essay focuses on a period of literary history that is often marginalized in accounts of women’s writing in English: the Middle Ages. It is a widely accepted view that there are only two women writers in English in the period before 1500, and therefore there is little to be said for an age (or ages) when women writers were so much an exception. Furthermore, the two medieval English women writers whose names are widely known, Julian of Norwich (1342/3-after 1416) and Margery Kempe (c.1373-after 1439), did not think of themselves as writers or authors. Nor were they responsible for literature as it is thought of today—they did not compose poetry, or romances, or fiction of any sort. Even these two ‘named’ women writers do not comfortably fit established evolutionary models of women’s literary history over the longue durée, with their emphases on the spread of literacy, the bias towards print culture, and the emergence of the woman poet, and ultimately of the professional author of drama or fiction. Yet the difficulty of locating how the medieval period fits in to literary history is not unique to women’s writing: medieval understandings of authorship, literature, and national identity, and the contexts and processes of writing and textual circulation were quite distinct from later periods and therefore deemed problematic more generally. This essay explores some of these issues and reflects on the difficulties we face writing a history of early women's writing

    Blowout of non-premixed turbulent jet flames with coflow under microgravity condition

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    The blowout behavior of non-premixed turbulent coflow jet flames under microgravity environment was studied experimentally by utilizing a 3.6 s drop tower. Variations of flames leading to liftoff as well as blowout were examined by varying the coflow velocity and compared with those obtained under the normal gravity condition. A modeling work was conducted to incorporate the effects of the gravity (buoyancy) and coflow velocity on blowout behavior. Major findings include: (1) the flame length in microgravity was longer than that in normal gravity and decreased with increasing coflow velocity. The flame in microgravity showed more intense yellow luminosity with larger sooting zone; (2) the flame liftoff height increased with increasing coflow velocity in both gravity levels. The flame base was closer to the burner in microgravity as compared with that in normal gravity; (3) the blowout velocity in microgravity was appreciably larger than that obtained in normal gravity; and (4) a physical model based on Damkohler number was developed by using similarity solutions to characterize the differences in the blowout limits considering both the coflow and gravity (buoyancy) effects. The proposed model can successfully predict the experimental data. This work provided new data and basic scaling analysis for blowout limit of non-premixed turbulent jet flames considering both the coflow and gravity (buoyancy) effects. (C) 2019 The Combustion Institute. Published by Elsevier Inc. All rights reserved

    Charles Berlitz, Author of "Doomsday," Takes Predictions

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    Charles Berlitz, author of "Doomsday," makes predictions that life will cease after 2000 A.D

    Luminescence luteinizing hormone/choriogonadotropin (LH/CG) bioassay : measurement of serum bioactive LH/CG during early pregnancy in human and macaque

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    Because of the microheterogeneities of gonadotropins, measurement of immunoreactivity of these glycoproteins does not necessarily reflect changes in their bioactivity. In addition, LH bioactivities in human samples analyzed by a rodent LH bioassay have been discordant with findings based on human granulosa-luteal cells. We have isolated a human LH/choriogonadotropin (CG) receptor cDNA and expressed the recombinant protein. Using 293 cells permanently transfected with the human LH receptor cDNA and a luciferase reporter gene driven by a cAMP-dependent promoter, we have developed a luminescence LH/CG bioassay. After cells were treated with human LH or CG for 20 h, luciferase activity was measured through use of a luminometer. Luciferase activity in the cells was increased in a dose-dependent manner. In contrast, treatment with FSH, thyroid-stimulating hormone, prolactin, growth hormone, adrenocorticotropin, insulin, prostaglandins, and several neurotransmitters had no effect. Because treatment with basic fibroblast growth factor (bFGF) caused significant increases in basal luciferase activity, a fixed amount of bFGF was included in all reactions. Incubation with 0.1 to 30 microliters serum from women during different physiological states stimulated the luciferase activity in parallel with the hCG standard curve. In 4 conception cycles, bioactive LH/hCG levels began to increase 2 wk after the midcycle LH surge, followed by a logarithmic increase from 22 days on. Due to the lack of a homologous RIA for measuring CG levels in monkeys, we analyzed serum bioactive monkey CG (mCG) in macaque during early pregnancy. Bioactive mCG was detected about 12 days after the midcycle LH surge and fertile mating and persisted until Days 21-23, followed by a decline.(ABSTRACT TRUNCATED AT 250 WORDS)</p
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