Circadian Entrainment Triggers Maturation of Human In Vitro Islets

Stem-cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human pluripotent stem cells (hPSCs) differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes. We find that enhancer potential is reset upon lineage commitment and show how pervasive epigenetic priming steers endocrine cell fates. Modeling islet differentiation and maturation regulatory circuits reveals genes critical for generating endocrine cells and identifies circadian control as limiting for in vitro islet function. Entrainment to circadian feeding/fasting cycles triggers islet metabolic maturation by inducing cyclic synthesis of energy metabolism and insulin secretion effectors, including antiphasic insulin and glucagon pulses. Following entrainment, hPSC-derived islets gain persistent chromatin changes and rhythmic insulin responses with a raised glucose threshold, a hallmark of functional maturity, and function within days of transplantation. Thus, hPSC-derived tissues are amenable to functional improvement by circadian modulation

Multisensory 3D saliency for artficial attention systems

In this paper we present proof-of-concept for a novel solution consisting of a short-term 3D memory for artificial attention systems, loosely inspired in perceptual processes believed to be implemented in the human brain. Our solution supports the implementation of multisensory perception and stimulus-driven processes of attention. For this purpose, it provides (1) knowledge persistence with temporal coherence tackling potential salient regions outside the field of view, via a panoramic, log-spherical inference grid; (2) prediction, by using estimates of local 3D velocity to anticipate the effect of scene dynamics; (3) spatial correspondence between volumetric cells potentially occupied by proto-objects and their corresponding multisensory saliency scores. Visual and auditory signals are processed to extract features that are then filtered by a proto-object segmentation module that employs colour and depth as discriminatory traits. We consider as features, apart from the commonly used colour and intensity contrast, colour bias, the presence of faces, scene dynamics and also loud auditory sources. Combining conspicuity maps derived from these features we obtain a 2D saliency map, which is then processed using the probability of occupancy in the scene to construct the final 3D saliency map as an additional layer of the Bayesian Volumetric Map (BVM) inference grid

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2fl/fl x Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl x Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process. RESULTS: Hig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl x Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes. CONCLUSIONS: We conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 degrees C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells

Social media and social class

Background: This paper explores the relationship between social class and social media use, and draws upon the work of Bourdieu examining class in terms of social, economic and cultural capital. The paper starts from a prior finding that those who predominantly only use social media formed a higher proportion of internet users from lower socio-economic groups. Data: Drawing on data from two nationally representative UK surveys the paper makes use of the Ofcom Media Literacy survey (n ≈ 1800 per annum) and the Department of Digital, Culture, Media and Sport Taking Part survey (n ≈ 10,000 per annum). Methods: Following Yates, et al. (2015a), five types of internet behaviour and eight types of internet user are identified utilising a principal components analysis and k-means clustering. These internet user types are then examined against measures of social, economic and cultural capital. Data on forms of cultural consumption and digital media use are examined using multiple correspondence analysis. Findings: The paper concludes that forms of digital media use are in correspondence with other social, cultural and economic aspects of social class status and contemporary social systems of distinction