Receptor Oligomerization in Family B1 of G-Protein-Coupled Receptors: Focus on BRET Investigations and the Link between GPCR Oligomerization and Binding Cooperativity

The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30–40% of all drug targets. During the last two decades, GPCR oligomerization has been extensively studied using methods like bioluminescence resonance energy transfer (BRET) and today, receptor–receptor interactions within the GPCR superfamily is a well-established phenomenon. Evidence of the impact of GPCR oligomerization on, e.g., ligand binding, receptor expression, and signal transduction indicates the physiological and pharmacological importance of these receptor interactions. In contrast to the larger and more thoroughly studied GPCR subfamilies A and C, the B1 subfamily is small and comprises only 15 members, including, e.g., the secretin receptor, the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality in family B1 GPCRs. One example of the functional effects of GPCR oligomerization is the facilitation of allosterism including cooperativity in ligand binding to GPCRs. Here, we review the currently available data on family B1 GPCR homo- and heteromerization, mainly based on BRET investigations. Furthermore, we cover the functional influence of oligomerization on ligand binding as well as the link between oligomerization and binding cooperativity

A synthetic data set to benchmark anti-money laundering methods

Bank transactions are highly confidential. As a result, there are no real public data sets that can be used to investigate and compare anti-money laundering (AML) methods in banks. This severely limits research on important AML problems such as efficiency, effectiveness, class imbalance, concept drift, and interpretability. To address the issue, we present SynthAML: a synthetic data set to benchmark statistical and machine learning methods for AML. The data set builds on real data from Spar Nord, a systemically important Danish bank, and contains 20,000 AML alerts and over 16 million transactions. Experimental results indicate that performance on SynthAML can be transferred to the real world. As use cases, we present and discuss open problems in the AML literature

Persona preparedness: a survey instrument for measuring the organizational readiness for deploying personas

User-centric design within organizations is crucial for developing information technology that offers optimal usability and user experience. Personas are a central user-centered design technique that puts people before technology and helps decision makers understand the needs and wants of the end-user segments of their products, systems, and services. However, it is not clear how ready organizations are to adopt persona thinking. To address these concerns, we develop and validate the Persona Readiness Scale (PRS), a survey instrument to measure organizational readiness for personas. After a 12-person qualitative pilot study, the PRS was administered to 372 professionals across different industries to examine its reliability and validity, including 125 for exploratory factor analysis and 247 for confirmatory factor analysis. The confirmatory factor analysis indicated a good fit with five dimensions: Culture readiness, Knowledge readiness, Data and systems readiness, Capability readiness, and Goal readiness. Higher persona readiness is positively associated with the respondents' evaluations of successful persona projects. Organizations can apply the resulting 18-item scale to identify areas of improvement before initiating costly persona projects towards the overarching goal of user-centric product development. Located at the cross-section of information systems and human-computer interaction, our research provides a valuable instrument for organizations wanting to leverage personas towards more user-centric and empathetic decision making about users

Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission

n rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling

Representativeness of the European social partner organisations : Sea fisheries sector

Aquesta publicació s'elabora a partir de les contribucions de cadascú dels membres nacionals que integren la Network of Eufound Correspondent. Pel cas d'Espanya la contribució ha estat realitzada per l'Alejandro GodinoThis study provides information allowing for an assessment of the representativeness of the actors involved in the European sectoral social dialogue committee for the sea fisheries sector. Their relative representativeness legitimises their right to be consulted, their role and effective participation in the European sectoral social dialogue and their capacity to negotiate agreements. The aim of Eurofound's representativeness studies is to identify the relevant national and European social partner organisations. This study identified the Association of National Organisations of Fishing Enterprises in the European Union (Europêche) (representing employers) and European Transport Workers' Federation (ETF) (representing employees) as the most representative European level social partner organisations in the sea fisheries sector. COPA-COGECA, representing employers in the primary sector, has also some representativeness in the sector

Representativeness of the European social partner organisations : Industrial cleaning sector

Aquesta publicació s'elabora a partir de les contribucions de cadascú dels membres nacionals que integren la Network of Eufound Correspondent. Pel cas d'Espanya la contribució ha estat realitzada per l'Alejandro GodinoThis study provides information to allow for an assessment of the representativeness of the actors involved in the European sectoral social dialogue committee for the industrial cleaning sector. Their relative representativeness legitimises their right to be consulted, their role and effective participation in the European sectoral social dialogue, and their capacity to negotiate agreements. The aim of Eurofound's representativeness studies is to identify the relevant national and European social partner organisations in the field of industrial relations in selected sectors in the EU Member States. This study identified the European Cleaning and Facility Services Industry (EFCI) (representing employers) and UNI Europa (representing employees) as the most representative European-level social partner organisations in the industrial cleaning sector

Representativeness of the European social partner organisations : human health sector

Aquesta publicació s'elabora a partir de les contribucions de cadascú dels membres nacionals que integren la Network of Eufound Correspondent. Pel cas d'Espanya la contribució ha estat realitzada per l'Oscar MolinaThis study provides information allowing for an assessment of the representativeness of the actors involved in the European sectoral social dialogue committee for the human health sector. Their relative representativeness legitimises their right to be consulted, their role and effective participation in the European sectoral social dialogue, and their capacity to negotiate agreements. The aim of Eurofound's studies on representativeness is to identify the relevant national and European social partner organisations in the field of industrial relations in the EU Member States. This study identified the European Federation of Public Service Unions (EPSU) - representing employees - and the European Hospital and Healthcare Employers' Association (HOSPEEM) - representing employers - as the most representative European-level social partner organisations in the human health sector. The member organisations of the European Confederation of Independent Trade Unions (CESI) and UNI Europa also organise employees in the sector in several Member States

Representativeness of the European social partner organisations : private security sector

Aquesta publicació s'elabora a partir de les contribucions de cadascú dels membres nacionals que integren la Network of Eufound Correspondent. Pel cas d'Espanya la contribució ha estat realitzada per l'Oscar MolinaThis study provides information allowing for an assessment of the representativeness of the actors involved in the European sectoral social dialogue committee for the private security sector. Their relative representativeness legitimises their right to be consulted, their role and effective participation in the European sectoral social dialogue and their capacity to negotiate agreements. The aim of Eurofound's representativeness studies is to identify the relevant national and European social partner organisations in the field of industrial relations in the EU Member States. This study identified the Confederation of European of Security Services (CoESS) (representing employers) and UNI Europa Private Security (representing employees) as the most representative European-level social partner organisations in the private security sector

Representativeness of the European social partner organisations : live performance sector

Aquesta publicació s'elabora a partir de les contribucions de cadascú dels membres nacionals que integren la Network of Eufound Correspondent. Pel cas d'Espanya la contribució ha estat realitzada per l'Alejandro GodinoThis study provides information allowing for an assessment of the representativeness of the actors involved in the European sectoral social dialogue committee for the live performance sector. Their relative representativeness legitimises their right to be consulted, their role and effective participation in the European sectoral social dialogue and their capacity to negotiate agreements. The aim of Eurofound's studies on representativeness is to identify the relevant national and European social partner organisations in the EU Member States. This study identified EURO-MEI, FIA and FIM - representing employees - and PEARLE* - representing employers - as the representative European-level social partner organisations in the live performance sector