Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells.

BACKGROUND: Diabetes mellitus is a common metabolic disorder characterized by dysfunction of insulin-secreting pancreatic beta-cells. MicroRNAs are important regulators of beta-cell activities. These non-coding RNAs have recently been discovered to exert their effects not only inside the cell producing them but, upon exosome-mediated transfer, also in other recipient cells. This novel communication mode remains unexplored in pancreatic beta-cells. In the present study, the microRNA content of exosomes released by beta-cells in physiological and physiopathological conditions was analyzed and the biological impact of their transfer to recipient cells investigated. RESULTS: Exosomes were isolated from the culture media of MIN6B1 and INS-1 derived 832/13 beta-cell lines and from mice, rat or human islets. Global profiling revealed that the microRNAs released in MIN6B1 exosomes do not simply reflect the content of the cells of origin. Indeed, while a subset of microRNAs was preferentially released in exosomes others were selectively retained in the cells. Moreover, exposure of MIN6B1 cells to inflammatory cytokines changed the release of several microRNAs. The dynamics of microRNA secretion and their potential transfer to recipient cells were next investigated. As a proof-of-concept, we demonstrate that if cel-miR-238, a C. Elegans microRNA not present in mammalian cells, is expressed in MIN6B1 cells a fraction of it is released in exosomes and is transferred to recipient beta-cells. Furthermore, incubation of untreated MIN6B1 or mice islet cells in the presence of microRNA-containing exosomes isolated from the culture media of cytokine-treated MIN6B1 cells triggers apoptosis of recipient cells. In contrast, exosomes originating from cells not exposed to cytokines have no impact on cell survival. Apoptosis induced by exosomes produced by cytokine-treated cells was prevented by down-regulation of the microRNA-mediating silencing protein Ago2 in recipient cells, suggesting that the effect is mediated by the non-coding RNAs. CONCLUSIONS: Taken together, our results suggest that beta-cells secrete microRNAs that can be transferred to neighboring beta-cells. Exposure of donor cells to pathophysiological conditions commonly associated with diabetes modifies the release of microRNAs and affects survival of recipient beta-cells. Our results support the concept that exosomal microRNAs transfer constitutes a novel cell-to-cell communication mechanism regulating the activity of pancreatic beta-cells

The spirit of sauna: legitimating the Finnish place brand

Purpose – The purpose of this paper is to investigate inhabitants of Finland and their continuing efforts to narrate a national identity within the constraints imposed by discursive meanings of Finnish culture through the experience of sauna. Design/methodology/approach – Data collection comprised semi-structured interviews with Finnish local residents and entrepreneurs; these were supplemented with secondary data including books, articles, advertisements and documents referencing sauna in the context of Finland. Findings – The analysis and interpretation by the authors show that the symbolic resource of sauna constitutes the legitimation of Finnish nation branding discourses at three levels: regulative, normative and cultural-cognitive; we label these sauna governance, communal identity creation and mythmaking, respectively. Originality/value – The research contribution reveals that nation branding discourses are also forms of legitimation work. Finnish nation branding discourses are interwoven with sauna as the symbolic resource of “Finnishness” and become conduits for the expression of discursive meanings. This demonstrates that institutional legitimacy is an intrinsic aspect of the ways place branding discourses can be used as a mode of governance (i.e. a policy instrument)

The Social context of motorcycle riding and the key determinants influencing rider behavior: A qualitative investigation

Objective: Given the increasing popularity of motorcycle riding and heightened risk of injury or death associated with being a rider, this study explored rider behaviour as a determinant of rider safety and, in particular, key beliefs and motivations which influence such behaviour. To enhance the effectiveness of future education and training interventions, it is important to understand riders’ own views about what influences how they ride. Specifically, this study sought to identify key determinants of riders’ behaviour in relation to the social context of riding including social and identity-related influences relating to the group (group norms and group identity) as well as the self (moral/personal norm and self-identity). ----- ----- Method: Qualitative research was undertaken via group discussions with motorcycle riders (n = 41). Results: The findings revealed that those in the group with which one rides represent an important source of social influence. Also, the motorcyclist (group) identity was associated with a range of beliefs, expectations, and behaviours considered to be normative. Exploration of the construct of personal norm revealed that riders were most cognizant of the “wrong things to do” when riding; among those issues raised was the importance of protective clothing (albeit for the protection of others and, in particular, pillion passengers). Finally, self-identity as a motorcyclist appeared to be important to a rider’s self-concept and was likely to influence their on-road behaviour. ----- ----- Conclusion: Overall, the insight provided by the current study may facilitate the development of interventions including rider training as well as public education and mass media messages. The findings suggest that these interventions should incorporate factors associated with the social nature of riding in order to best align it with some of the key beliefs and motivations underpinning riders’ on-road behaviours

“Alexa, order me a pizza!”: The mediating role of psychological power in the consumer–voice assistant interaction

This article investigates the consumer-voice assistant (VA) interaction in the context of food and beverage purchase choices and the role that psychological power plays in the consumer decisionmaking process. A series of experimental studies demonstrate that both involvement and the psychological condition of power meditate consumers’ willingness to purchase. As a result, we find that consumers are more likely to purchase low involvement than high-involvement products through VA technology, particularly when experiencing high-power states. This research broadens our understanding of the role of VAs and their ability to shape the consumer decision-making process. With an explicit focus on power, this study illustrates how the success of voice commerce may largely rest on the promotion of low-involvement products that enable high-power psychological conditions which drive willingness to purchase

A large-momentum-transfer matter-wave interferometer to measure the effect of gravity on positronium

This paper reports the study of a new interferometric configuration to measure the effect of gravity on positronium. A Mach–Zehnder matter-wave interferometer has been designed to operate with single-photon transitions and to transfer high momentum to a 200 eV positronium beam. The work shows the results and methods used to simulate the interferometer and estimate the operating parameters and the time needed to perform the experiment. It has been estimated that within less than 1 year, the acquisition time is sufficient to achieve a 10% accuracy level in measuring positronium gravitational acceleration, even with a poorly collimated beam, which is significant for theoretical models describing matter–antimatter symmetry. These results pave the way for single photon transition large momentum transfer interferometry with fast atomic beams, which is particularly useful for studies with antimatter and unstable atoms

Loss and revival of coherence in the interaction between a positron beam and a photon field

We study the interaction between a positron beam in the single-particle regime in an interferometric configuration and a microwave electromagnetic field. We discuss the conditions under which quantum interference can be affected by the field and we outline its possible experimental study in the framework of QUantum interferometry and gravitation with Positrons and LASers (QUPLAS) experiment

AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons

Functional as well as structural alterations in mitochondria size, shape and distribution are precipitating, early events in progression of Alzheimer's Disease (AD). We reported that a 20\u201322 kDa NH2-tau fragment (aka NH2htau), mapping between 26 and 230 amino acids of the longest human tau isoform, is detected in cellular and animal AD models and is neurotoxic in hippocampal neurons. The NH2htau \u2013but not the physiological full-length protein\u2013 interacts with A\u3b2 at human AD synapses and cooperates with it in inhibiting the mitochondrial ANT-1-dependent ADP/ATP exchange. Here we show that the NH2htau also adversely affects the interplay between the mitochondria dynamics and their selective autophagic clear- ance. Fragmentation and perinuclear mislocalization of mitochondria with smaller size and density are early found in dying NH2htau-expressing neurons. The specific effect of NH2htau on quality control of mitochondria is accompanied by (i) net reduction in their mass in correlation with a general Parkin- mediated remodeling of membrane proteome; (ii) their extensive association with LC3 and LAMP1 autoph- agic markers; (iii) bioenergetic deficits and (iv) in vitro synaptic pathology. These results suggest that NH2htau can compromise the mitochondrial biology thereby contributing to AD synaptic deficits not only by ANT-1 inactivation but also, indirectly, by impairing the quality control mechanism of these organelles