Protein phosphatase 1c associated with the cardiac sodium calcium exchanger1 regulates its activity by dephosphorylating serine 68 phosphorylated phospholemman

The sodium (Na+)-calcium (Ca2+) exchanger 1 (NCX1) is an important regulator of intracellular Ca2+ homeostasis. Serine 68-phosphorylated phospholemman (pSer-68-PLM) inhibits NCX1 activity. In the context of Na+/K+-ATPase (NKA) regulation, pSer-68-PLM is dephosphorylated by protein phosphatase 1 (PP1). PP1 also associates with NCX1; however, the molecular basis of this association is unknown. In this study, we aimed to analyze the mechanisms of PP1 targeting to the NCX1-pSer-68-PLM complex and hypothesized that a direct and functional NCX1-PP1 interaction is a prerequisite for pSer-68-PLM dephosphorylation. Using a variety of molecular techniques, we show that PP1 catalytic subunit (PP1c) co-localized, co-fractionated, and co-immunoprecipitated with NCX1 in rat cardiomyocytes, left ventricle lysates, and HEK293 cells. Bioinformatic analysis, immunoprecipitations, mutagenesis, pulldown experiments, and peptide arrays constrained PP1c anchoring to the K(I/V)FF motif in the first Ca2+ binding domain (CBD) 1 in NCX1. This binding site is also partially in agreement with the extended PP1-binding motif K(V/I)FF-X5–8Φ1Φ2-X8–9-R. The cytosolic loop of NCX1, containing the K(I/V)FF motif, had no effect on PP1 activity in an in vitro assay. Dephosphorylation of pSer-68-PLM in HEK293 cells was not observed when NCX1 was absent, when the K(I/V)FF motif was mutated, or when the PLM- and PP1c-binding sites were separated (mimicking calpain cleavage of NCX1). Co-expression of PLM and NCX1 inhibited NCX1 current (both modes). Moreover, co-expression of PLM with NCX1(F407P) (mutated K(I/V)FF motif) resulted in the current being completely abolished. In conclusion, NCX1 is a substrate-specifying PP1c regulator protein, indirectly regulating NCX1 activity through pSer-68-PLM dephosphorylation

Media Systems and the Political Information Environment: A Cross-National Comparison

To express attitudes and act according to their self-interest, citizens need relevant, up-to-date information about current affairs. But has the increased commercialization in the media market increased or decreased the flow of political information? Hallin and Mancini stress that the existing empirical evidence is fragmented and that this question therefore has been difficult to answer. In this article the authors present new data that allow them to systematically examine how the flow of political information on TV occurs across six Western countries during a thirty-year period. The authors find that the flow of political information through TV varies according to the degree of commercialization. The flow of news and current affairs is lowest in the most commercially oriented television system and among the commercial TV channels. There is however important cross-national variation even within similar media systems. The authors’ data do not suggest a convergence toward the liberal system when it comes to the political information environment on TV. Rather, what strikes them is how strongly resistant some European countries have been to subordinating the needs of democracy to profit making

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Re: en ny samhällssektor spirar

Resurser och hållbarhet är nära förknippade. Hållbarhet innebär att hushålla med resurser - materiella, miljömässiga och mänskliga. Och hushållning är per definition kärnan i ekonomi. Man börjar alltmer se framväxten av en hel arsenal av verktyg och förhållnings- och angreppssätt för att bygga hållbarhet. Detta förenas av ett synsätt att det som hitintills setts  om avfall och värdelöst, och rent utav besvärligt att ta hand om, nu blir en värdefull resurs. Det glömda och gömda kommer åter. Faktum är att många ord och begrepp kring detta börjar på just åter- eller re- . Internationellt talar man om Redesign, Recycling, Remake, Recycle, Recraft, Reuse, Recreate, Reclaim, Reduce, Repair, Refashion. Vad är då allt detta? Ja, vill man dra det långt, är det inte mindre än framväxten av ett nyvunnet sätt att tänka, ja av en ny samhällssektor, en bransch och en industri,  sammanbundet av filosofin att återanvändningen, spillminskningen, vidarebruket, efterlivet anses som viktiga faktorer för ett miljömedvetet samhälle. Re: blir paraplytermen för detta. I denna antologi av forskare från skilda discipliner vid Högskolan i Borås lyfts ett antal av dessa begrepp inom Re: fram