5,809 research outputs found
Differential expression and functional characterization of luteinizing hormone receptor splice variants in human luteal cells : Implications for luteolysis
No full textThe human LH receptor (LHR) plays a key role in luteal function and the establishment of pregnancy through its interaction with the gonadotropins LH and human chorionic gonadotropin. We previously identified four splice variants of the LHR in human luteinized granulosa cells (LGCs) and corpora lutea (CL). Real-time quantitative PCR revealed that expression of the full-length LHR (LHRa) and the most truncated form (LHRd) changed significantly in CL harvested at different stages of the ovarian cycle (P < 0.01, ANOVA). LHRa expression was reduced in the late luteal CL (P<0.05). Conversely, an increase in LHRd expression was observed in the late luteal CL (P<0.01). Chronic manipulation of human chorionic gonadotropin in LGC primary cultures supported the in vivo findings. LHRd encodes a protein lacking the transmembrane and carboxyl terminal domains. COS-7 cells expressing LHRd were unable to produce cAMP in response to LH stimulation. COS-7 cells coexpressing LHRd and LHRa also failed to generate cAMP in response to LH, suggesting that this truncated form has a negative effect on the signaling of LHRa. Immunofluorescence staining ofLGC and COS-7 cells implied that there is a reduction in cell surface expression ofLHRa when LHRd is present. Overall, these results imply expression of LHR splice variants is regulated in the human CL. Furthermore, during functional luteolysis a truncated variant could modulate the cell surface expression and activity of full-length LHR.Peer reviewe
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
No full textG 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
No full textHow 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 textHow 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
No full textThe 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
No full textCharles Berlitz, author of "Doomsday," makes predictions that life will cease after 2000 A.D
Reduction of Free Radicals and Endotoxin by Conjugated Linoleic Acid Loaded in an In Situ-Synthesized Poly(N-isopropyl acrylamide) Thin Layer
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The Role of RP3V Kisspeptin Neurons in Inducing the LH Surge in Female Mice
No full textIn mammals, fertility is intricately linked to the hypothalamic-pituitary-gonadal (HPG) axis, beginning with GnRH neurons in the hypothalamus. These neurons stimulate the pituitary to release LH and FSH hormones, thereby activating the gonads. Ovulation, crucial for female fertility, is triggered by an estrogen-induced GnRH/LH surge. Although the exact mechanisms of the LH surge are not fully understood, Kiss1 neurons, which synthesize kisspeptin, are believed to play a pivotal role. Specifically, research suggests that Kiss1 neurons in the hypothalamic rostral periventricular area of the third ventricle (RP3V) are key in mediating estrogen's positive feedback, which induces the preovulatory GnRH/LH surge. However, their direct involvement in ovulation has not been functionally validated. This study employs THCre/KissFlox transgenic mice to investigate the consequences of knocking down kisspeptin in RP3V neurons on the processes that drive ovulation. By reducing kisspeptin levels in the RP3V region by 50-70%, we observed a diminished estrogen-induced LH surge magnitude and likelihood, although this did not directly cause infertility. We then compared ovary-intact mice with ovariectomized (OVX) mice, both receiving estrogen implants, to further elucidate the roles of ovaries in LH surge regulation. Notably, a significant proportion of ovary-intact mice did not show an estrogen-induced LH surge, unlike the OVX mice, and the increased activation levels of RP3V Kiss1 neurons in OVX mice again implied the role of RP3V Kiss1 neurons in initiating the LH surge. In conclusion, our findings reinforce the hypothesis that RP3V kisspeptin neurons are crucial for initiating the estrogen-induced LH surge, with their inhibition potentially leading to a reduced or absent surge. This research contributes to a deeper understanding of the mechanisms underlying female fertility, in particular the processes that trigger ovulation
Involvement of the endogenous opioid peptides in suckling-induced inhibition of LH release
No full textTypescript (photocopy).Two studies were conducted to further understand the involvement of the endogenous opioid peptides (EOPs) in suckling-induced inhibition of LH release. Experiment A in the first study was designed to evaluate the effect of naloxone (NAL) infusion (1.0 mg/kg bw/h) on serum LH and hypothalamic LHRH content in 1 week ovariectomized suckled (8 pups/animal) rats after 18 h pup removal, and after 18 h resuckling. Pup removal resulted in an increase (p0.10) serum LH in suckled or nonsuckled rats. Hypothalamic LHRH content in NAL-treated rats was not changed upon pup removal or subsequent resuckling. Experiment B was designed to evaluate the effect of NAL on serum LH and hypothalamic HRH content in suckled rats. Serum LH increased (p0.10) LH release nor did it influence (p>0.10) hypothalamic LHRH content. The second study was designed to evaluate the effect of NAL infusion (1.0 mg/kg bw/h for 7 days) in ovariectomized suckled rats, and ovariectomy on LHRH neuron morphology using immunocytochemistry. NAL did not influence LHRH immunoreactivity in the infundibulum (INF) nor was it able to influence neuronal morphology. In contrast, rats ovariectomized for 3 weeks had a greater proportion (48% vs 25%, respectively) of smooth LHRH neurons compared to diestrous rats..
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