Glycogen synthase kinases 3α and 3β in cardiac myocytes: regulation and consequences of their inhibition

Inhibition of glycogen synthase kinase 3β (GSK3β) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3α (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3β in cardiac myocytes. Although endothelin increases phosphorylation of GSK3 and decreases its activity, the response is less than that induced by insulin (which does not promote cardiac myocyte hypertrophy). GSK3 phosphorylation induced by endothelin requires signalling through the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade and not the PKB/Akt pathway, whereas the reverse is true for insulin. Cardiac myocyte hypertrophy involves changes in morphology, and in gene and protein expression. The potent GSK3 inhibitor 1-azakenpaullone increases myocyte area as a consequence of increased cell length whereas phenylephrine increases both length and width. Azakenpaullone or insulin promotes AP1 transcription factor binding to an AP1 consensus oligonucleotide, but this was significantly less than that induced by endothelin and derived principally from increased binding of JunB protein, the expression of which was increased. Azakenpaullone promotes significant changes in gene expression (assessed by Affymetrix microarrays), but the overall response is less than with endothelin and there is little overlap between the genes identified. Thus, although GSK3 may contribute to cardiac myocyte hypertrophy in some respects (and presumably plays an important role in myocyte metabolism), it does not appear to contribute as significantly to the response induced by endothelin as has been maintained

Evidence of Multiple r-Process Sites in the Early Galaxy: New Observations of CS 22892-052

First results are reported of a new abundance study of neutron-capture elements in the ultra-metal-poor (UMP; [Fe/H] = -3.1) halo field giant star CS 22892-052. Using new high resolution, high signal-to-noise spectra, abundances of more than 30 neutron-capture elements (Z>30) have been determined. Six elements in the 40<Z<56 domain (Nb, Ru, Rh, Pd, Ag and Cd) have been detected for the first time in a UMP star. Abundances are also derived for three of the heaviest stable elements (Os, Ir, and Pb). A second transition of thorium, Th{4086}, confirms the abundance deduced from the standard Th{4019} line, and an upper limit to the abundance of uranium is established from the absence of the U{3859} line. As found in previous studies, the abundances of the heavier (Z>=56) stable neutron-capture elements in CS 22892-052 match well the scaled solar system r-process abundance distribution. From the observed Th abundance, an average age of ~= 16 +/- 4 Gyr is derived for cs22892-052, consistent with the lower age limit of ~= 11 Gyr derived from the upper limit on the U abundance. The concordance of scaled solar r-process and CS 22892-052 abundances breaks down for the lighter neutron-capture elements, supporting previous suggestions that different r-process production sites are responsible for lighter and heavier neutron-capture elements.Comment: To be published in the Astrophysical Journal Letter

Theology, News and Notes - Vol. 39, No. 03

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1114/thumbnail.jp

Theology, News and Notes - Vol. 41, No. 02

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1120/thumbnail.jp

The Impact of The European Enlargement and CAP Reforms on Agricultural Markets. Much Ado about Nothing?

We analyze the effects of the 2004 CAP reform and EU enlargement on European and world agricultural markets. We compare the results from a CAP reform only and a CAP reform plus enlargement scenarios to a no-enlargement baseline implementing Agenda 2000 CAP policies. We utilize the Food and Agricultural Policy Research Institute's policy analysis model to simulate the effects of CAP reform and EU enlargement on production, consumption, and trade for the EU, its New Member States (NMS), and major players in world agricultural markets. The model is a partial-equilibrium model of world agricultural markets including important producer and consumer countries in world livestock and products, dairy, grains, oilseeds and products, cotton and sugar markets. Each country's commodity sectors are modeled with structural equations which incorporate all important policy parameters. With prices in most commodities in the NMS historically below EU-15 prices accession leads to substantial price increases for many commodities in the NMS. Higher prices stimulate production and dampen consumption in the NMS, and trade between the new members and the EU-15 increases. Prices in the EU-15 decrease moderately. The impact of the two reforms on world markets is negligible. The CAP reforms have their greatest impact in the EU-15 markets for meats, rice, rapeseed, and dairy products. CAP reforms without enlargement generate a small increase in world and EU commodity prices.CAP, trade reform, policy reform, enlargement, new member states, European Union, Agricultural and Food Policy, Marketing, F1, Q17, Q18,

Exploring the costs and outcomes of sexually transmitted infection (STI) screening interventions targeting men in football club settings: preliminary cost-consequence analysis of the SPORTSMART pilot randomised controlled trial

Background: The objective of this study was to compare the costs and outcomes of two sexually transmitted infection (STI) screening interventions targeted at men in football club settings in England, including screening promoted by team captains. Methods: A comparison of costs and outcomes was undertaken alongside a pilot cluster randomised control trial involving three trial arms: (1) captain-led and poster STI screening promotion; (2) sexual health advisor-led and poster STI screening promotion and (3) poster-only STI screening promotion (control/comparator). For all study arms, resource use and cost data were collected prospectively. Results: There was considerable variation in uptake rates between clubs, but results were broadly comparable across study arms with 50% of men accepting the screening offer in the captain-led arm, 67% in the sexual health advisor-led arm and 61% in the poster-only control arm. The overall costs associated with the intervention arms were similar. The average cost per player tested was comparable, with the average cost per player tested for the captain-led promotion estimated to be £88.99 compared with £88.33 for the sexual health advisor-led promotion and £81.87 for the poster-only (control) arm. Conclusions: Costs and outcomes were similar across intervention arms. The target sample size was not achieved, and we found a greater than anticipated variability between clubs in the acceptability of screening, which limited our ability to estimate acceptability for intervention arms. Further evidence is needed about the public health benefits associated with screening interventions in non-clinical settings so that their cost-effectiveness can be fully evaluated