31 resultados para Typesetting.


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Mode of access: Internet.

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Доклад, поместен в сборника на Националната конференция "Образованието в информационното общество", Пловдив, май, 2010 г.

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Доклад, поместен в сборника на Националната конференция "Образованието в информационното общество", Пловдив, май, 2012 г.

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Copyright ©ERS 2014.

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Date of Acceptance: 12/12/2014 Support statement: This study was funded by the Wellcome Trust (Ref 092121/Z/10/Z), who played no role in its conception, methods, analysis or interpretation. Funding information for this article has been deposited with FundRef.

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Copyright ©ERS 2014.

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Date of Acceptance: 12/12/2014 Support statement: This study was funded by the Wellcome Trust (Ref 092121/Z/10/Z), who played no role in its conception, methods, analysis or interpretation. Funding information for this article has been deposited with FundRef.

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Peer reviewed

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Inscription: Verso: Women at work: miscellaneous occupations.

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Dear Philip,

Thank you for adding your record to Pure. We notice that as of yet you have not uploaded your accepted manuscript for this publication.

As you may be aware HEFCE require that the accepted manuscripts of all journal articles and conference proceedings with an ISSN accepted from the 1st April 2016 are uploaded to Pure within 3 months of early online publication to ensure eligibility for the post 2014 REF.

The accepted manuscript is the final accepted version after changes from peer review have been incorporated. It is usually a Word or plain text file without publisher logos and prior to copy-editing and typesetting applied by the publisher.

If you have this version, I would be grateful if you could upload it to the record, selecting "Accepted author manuscript (post print)" from the document version drop down menu. If you have not done so already, please add your date of acceptance. Library staff will apply a copyright statement and any embargo required by the publisher.

Please contact me if you have any questions or require further information.

Kind regards,


Mark

Open Access Team

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Retinitis pigmentosa (RP) is a degenerative retinal disease leading to photoreceptor cell loss. In 2011, our group identified the synthetic progesterone ‘Norgestrel’ as a potential treatment for RP. Subsequent research showed Norgestrel to work through progesterone receptor membrane component 1 (PGRMC1) activation and upregulation of neuroprotective basic fibroblast growth factor (bFGF). Using trophic factor deprivation of 661W photoreceptor-like cells, we aimed to further elucidate the mechanism leading to Norgestrel-induced neuroprotection. In the present manuscript, we show by flow cytometry and live-cell immunofluorescence that Norgestrel induces an increase in cytosolic calcium in both healthy and stressed 661Ws over 24h. Specific PGRMC1 inhibition by AG205 (1 μM) showed this rise to be PGRMC1-dependent, primarily utilising calcium from extracellular sources, for blockade of L-type calcium channels by verapamil (50 μM) prevented a Norgestrel-induced calcium influx in stressed cells. Calcium influx was also shown to be bFGF-dependent, for siRNA knock down of bFGF prevented Norgestrel-PGRMC1 induced changes in cytosolic calcium. Notably, we demonstrate PGRMC1-activation is necessary for Norgestrel-induced bFGF upregulation. We propose that Norgestrel protects through the following pathway: binding to and activating PGRMC1 expressed on the surface of photoreceptor cells, PGRMC1 activation drives bFGF upregulation and subsequent calcium influx. Importantly, raised intracellular calcium is critical to Norgestrel's protective efficacy, for extracellular calcium chelation by EGTA abrogates the protective effects of Norgestrel on stressed 661W cells in vitro.