CCN5/WISP2 and metabolic diseases.

This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s12079-017-0437-zObesity and type 2 diabetes increase worldwide at an epidemic rate. It is expected that by the year 2030 around 500 million people will have diabetes; predominantly type 2 diabetes. The CCN family of proteins has become of interest in both metabolic and other common human diseases because of their effects on mesenchymal stem cell (MSCs) proliferation and differentiation as well as being important regulators of fibrosis. We here review current knowledge of the WNT1 inducible signaling pathway protein 2 (CCN5/WISP2). It has been shown to be an important regulator of both these processes through effects on both the canonical WNT and the TGFβ pathways. It is also under normal regulation by the adipogenic commitment factor BMP4, in contrast to conventional canonical WNT ligands, and allows MSCs to undergo normal adipose cell differentiation. CCN5/WISP2 is highly expressed in, and secreted by, MSCs and is an important regulator of MSCs growth. In a transgenic mouse model overexpressing CCN5/WISP2 in the adipose tissue, we have shown that it is secreted and circulating in the blood, the mice develop hypercellular white and brown adipose tissue, have increased lean body mass and enlarged hypercellular hearts. Obese transgenic mice had improved insulin sensitivity. Interestingly, the anti-fibrotic effect of CCN5/WISP2 is protective against heart failure by inhibition of the TGFβ pathway. Understanding how CCN5/WISP2 is regulated and signals is important and may be useful for developing new treatment strategies in obesity and metabolic diseases and it can also be a target in regenerative medicine.The studies in the authors’ laboratory are supported by grants from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement (n° 608765), Henning and Johan Throne- Holst’s foundation for the promotion of scientific research, the Medical Research Council, Torsten Söderberg Foundation, Novo Nordisk Foundation, EFSD, Swedish Diabetes Foundation, Swedish ALF funds, Edgar Sjölund Foundation, Wilhelm and Martina Lundgren’s Foundation, the Magnus Bergvall Foundation, Lisa and Johan Grönberg Foundation, Göteborgs Diabetesförening, Sigurd and Elsa Golje’s Foundation, and the EU’s FP7 program (n°607842)

f-electron hybridised Fermi surface in magnetic field-induced metallic YbB12

The nature of the Fermi surface observed in the recently discovered family of unconventional insulators starting with SmB6 is a subject of intense inquiry. Here we shed light on this question by accessing quantum oscillations in the high magnetic fieldinduced metallic regime above ≈47 T in YbB12, which we compare with the unconventional insulating regime. In the field-induced metallic regime, we find prominent quantum oscillations in the electrical resistivity characterised by multiple frequencies and heavy effective masses. The close similarity in Lifshitz-Kosevich low-temperature growth of quantum oscillation amplitude in insulating YbB12 to field-induced metallic YbB12, points to an origin of quantum oscillations in insulating YbB12 from in-gap neutral low energy excitations. Higher frequency Fermi surface sheets of heavy quasiparticle effective mass emerge in the field-induced metallic regime of YbB12 in addition to multiple heavy Fermi surface sheets observed in both insulating and metallic regimes. f-electron hybridisation is thus observed to persist from the unconventional insulating to the field-induced metallic regime of YbB12, in contrast to the unhybridised conduction electron Fermi surface observed in unconventional insulating SmB6. Our findings thus require an alternative model for YbB12, of neutral in-gap low energy excitations, wherein the f-electron hybridisation is retained

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Proceedings of the 29th EG-ICE International Workshop on Intelligent Computing in Engineering

This publication is the Proceedings of the 29th EG-ICE International Workshop on Intelligent Computing in Engineering from July 6-8, 2022. The EG-ICE International Workshop on Intelligent Computing in Engineering brings together international experts working on the interface between advanced computing and modern engineering challenges. Many engineering tasks require open-world resolution of challenges such as supporting multi-actor collaboration, coping with approximate models, providing effective engineer-computer interaction, search in multi-dimensional solution spaces, accommodating uncertainty, including specialist domain knowledge, performing sensor-data interpretation and dealing with incomplete knowledge. While results from computer science provide much initial support for resolution, adaptation is unavoidable and most importantly, feedback from addressing engineering challenges drives fundamental computer-science research. Competence and knowledge transfer goes both ways. &nbsp

Proceedings of the 29th EG-ICE International Workshop on Intelligent Computing in Engineering

This publication is the Proceedings of the 29th EG-ICE International Workshop on Intelligent Computing in Engineering from July 6-8, 2022. The EG-ICE International Workshop on Intelligent Computing in Engineering brings together international experts working on the interface between advanced computing and modern engineering challenges. Many engineering tasks require open-world resolution of challenges such as supporting multi-actor collaboration, coping with approximate models, providing effective engineer-computer interaction, search in multi-dimensional solution spaces, accommodating uncertainty, including specialist domain knowledge, performing sensor-data interpretation and dealing with incomplete knowledge. While results from computer science provide much initial support for resolution, adaptation is unavoidable and most importantly, feedback from addressing engineering challenges drives fundamental computer-science research. Competence and knowledge transfer goes both ways. &nbsp

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A potential new target for patients with kidney diseases

Treatment of patients with nephrotic syndrome (NS) is currently unspecific and directed at ameliorating the symptoms rather than eliminating the cause. NS is actually a multitude of glomerular diseases characterized by poorly understood disease mechanisms and symptoms that include proteinuria, hypoalbuminemia and edema. Originally described in the 1950s, treatment of NS with adrenocorticotropic hormone (ACTH) was rediscovered lately and its potentially beneficial effects on proteinuria and glomerular function have been studied in patients with different nephrotic diseases. Our research group has shown that the effects of ACTH treatment are mediated through cells in the glomerulus. Thus, the melanocortin 1 receptor (MC1R) was found to be colocalizing with the podocyte marker synaptopodin. Treatment with MC1R specific agonists had beneficial effects in an experimental model of membranous nephropathy, Passive Heymann Nephritis (PHN). The aims of this thesis have therefore been to examine the intracellular signaling pathways and beneficial mechanisms following MC1R stimulation both in vitro and in vivo. The hypothesis is that MC1R stimulation activates a number of beneficial effects in podocytes and stabilizes the actin cytoskeleton. To study these mechanisms, we performed experiments with MC1R selective agonists in the in vivo models of nephrotic syndrome; PHN and adriamycin nephropathy (AN). MC1R stimulation had ameliorating effects in the PHN model, but not in the AN model. In addition, we did in vitro experiments in order to analyze the intracellular effects induced by MC1R stimulation, and to perform a large-scale pathway analysis. MC1R stimulation induced a number of protective effects in podocytes, including increased catalase activity, decreased oxidative stress and protection against apoptosis. Furthermore, MC1R stimulation affected the actin cytoskeleton by inducing RhoA activity and increasing stress fiber formation. Subsequently, the MC1R stimulation had protective effects in both the puromycin and protamine sulfate in vitro models. We conclude that MC1R stimulation has beneficial effects in different models of NS through activation of endogenous protective pathways and by stabilizing of the actin cytoskeleton. Building on these results, we believe that it is possible to create new, specific drugs with minimal side effects to treat patients with nephrotic syndromes in the future