Cinque Terre is one of the most picturesque regions in Italy. These steep, colorful fishing villages perched on seaside cliffs of the Italian Riviera will take your breath away! There are 5 towns of Cinque Terre: Monterosso al Mare, Vernazza, Corniglia, Manarola, and Riomaggiore. Here you’ll find my recommendations for all five towns, plus the […]

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3.6 million will pay with crypto in US; payment value to spike 70% in 2022   April 20, 2022 (New York, NY) – Cryptocurrency usage will continue its meteoric rise, […]

G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs.

Independent Thinking: Insurrections and elections in Brazil and the US Audio NCapeling 20 January 2023

Episode 11 examines disinformation in the US and Brazil, the role played by social media platforms, and how conspiracy theories percolate online.

The storming in Brasilia of government institutions by supporters of former president Jair Bolsonaro echoed the events seen at the US Capitol building on 6 January 2021. This week’s guests discuss the impact on Brazil.

The panel also examines the state of politics in the US going into 2023. How are things shaping up for Joe Biden’s presidency after the mid-terms now that a new Congress has been sworn in? And what are the challenges being faced more broadly by the American body politic two years on from the insurrection at Capitol Hill.

Joining guest host Leslie Vinjamuri this week from Chatham House is Christopher Sabatini, senior research fellow for Latin America, Serusha Govender, the Mo Ibrahim Foundation academy fellow, and Alex Krasodomski, senior research associate at the Digital Society Initiative.