Perinatal Exposure to Bisphenol A Alters Early Adipogenesis in the Rat

BACKGROUND: The causes of the current obesity pandemic have not been fully elucidated. Implication of environmental endocrine disruptors such as bisphenol A (BPA) on adipose tissue development has been poorly investigated. OBJECTIVES: The aim of the present study was to evaluate the effects of perinatal exposure to BPA on early adipose storage at weaning. METHODS: Pregnant Sprague-Dawley rats had access to drinking water containing 1 mg/L BPA from day 6 of gestation through the end of lactation. Pups were weaned on postnatal day (PND) 21. At that time, we investigated perigonadal adipose tissue of pups (weight, histology, gene expression). For the remaining animals, we recorded body weight and food intake for animals on either standard chow or a high-fat diet. RESULTS: Gestational exposure to BPA did not alter the sex ratio or litter size at birth. On PND1, the weight of male and female BPA-exposed pups was increased. On PND21, body weight was increased only in females, in which parametrial white adipose tissue (pWAT) weight was increased about 3-fold. This excess of pWAT was associated with adipocyte hypertrophy and overexpression of lipogenic genes such as C/EBP-alpha (CAAT enhancer binding protein alpha), PPAR-gamma (peroxisome proliferator-activated receptor gamma), SREBP-1C (sterol regulatory element binding protein-1C), LPL (lipoprotein lipase), FAS (fatty acid synthase), and SCD-1 (stearoyl-CoA desaturase 1). In addition, gene expression of SREBP-1C, FAS, and ACC (acetyl-CoA carboxylase) was also increased in liver from BPA-exposed females at PND21, without a change in circulating lipids and glucose. After weaning, perinatal BPA exposure predisposed to overweight in a sex- and diet-dependent manner. We observed no change in food intake due to perinatal BPA exposure in rats on either standard chow or a high-fat diet. CONCLUSIONS: Perinatal exposure to a low dose of BPA increased adipogenesis in females at weaning. Adult body weight may be programmed during early life, leading to changes dependent on the sex and the nutritional status. Although further studies are required to understand the mechanisms of BPA action in early life, these results are particularly important with regard to the increasing prevalence of childhood obesity and the context-dependent action of endocrine disruptors

Offscreen and in the chair next to your: conversational agents speaking through actual human bodies

his paper demonstrates how to interact with a conversational agent that speaks through an actual human body face-to-face and in person (i.e., offscreen). This is made possible by the cyranoid method: a technique involving a human person speech shadowing for a remote third-party (i.e., receiving their words via a covert audio-relay apparatus and repeating them aloud in real-time). When a person shadows for an artificial conversational agent source, we call the resulting hybrid an “echoborg.” We report a study in which people encountered conversational agents either through a human shadower face-to-face or via a text interface under conditions where they assumed their interlocutor to be an actual person. Our results show that the perception of a conversational agent is dramatically altered when the agent is voiced by an actual, tangible person. We discuss the potential implications this methodology has for the development of conversational agents and general person perception research

Consciousness in Artificial Intelligence: Insights from the Science of Consciousness

Whether current or near-term AI systems could be conscious is a topic of scientific interest and increasing public concern. This report argues for, and exemplifies, a rigorous and empirically grounded approach to AI consciousness: assessing existing AI systems in detail, in light of our best-supported neuroscientific theories of consciousness. We survey several prominent scientific theories of consciousness, including recurrent processing theory, global workspace theory, higher-order theories, predictive processing, and attention schema theory. From these theories we derive "indicator properties" of consciousness, elucidated in computational terms that allow us to assess AI systems for these properties. We use these indicator properties to assess several recent AI systems, and we discuss how future systems might implement them. Our analysis suggests that no current AI systems are conscious, but also suggests that there are no obvious technical barriers to building AI systems which satisfy these indicators

Are intuitions about moral relevance susceptible to framing effects?

Various studies have reported that moral intuitions about the permissibility of acts are subject to framing effects. This paper reports the results of a series of experiments which further examine the susceptibility of moral intuitions to framing effects. The main aim was to test recent speculation that intuitions about the moral relevance of certain properties of cases might be relatively resistent to framing effects. If correct, this would provide a certain type of moral intuitionist with the resources to resist challenges to the reliability of moral intuitions based on such framing effects. And, fortunately for such intuitionists, although the results can’t be used to mount a strident defence of intuitionism, the results do serve to shift the burden of proof onto those who would claim that intuitions about moral relevance are problematically sensitive to framing effects

Pancreatic Transcription Factors Containing Protein Transduction Domains Drive Mouse Embryonic Stem Cells towards Endocrine Pancreas

Protein transduction domains (PTDs), such as the HIV1-TAT peptide, have been previously used to promote the uptake of proteins into a range of cell types, including stem cells. Here we generated pancreatic transcription factors containing PTD sequences and administered these to endoderm enriched mouse embryonic stem (ES) cells under conditions that were designed to mimic the pattern of expression of these factors in the developing pancreas. The ES cells were first cultured as embryoid bodies and treated with Activin A and Bone morphogenetic protein 4 (BMP4) to promote formation of definitive endoderm. Cells were subsequently plated as a monolayer and treated with different combinations of the modified recombinant transcription factors Pdx1 and MafA. The results demonstrate that each transcription factor was efficiently taken up by the cells, where they were localized in the nuclei. RT-qPCR was used to measure the expression levels of pancreatic markers. After the addition of Pdx1 alone for a period of five days, followed by the combination of Pdx1 and TAT-MafA in a second phase, up-regulation of insulin 1, insulin 2, Pdx1, Glut2, Pax4 and Nkx6.1 was observed. As assessed by immunocytochemistry, double positive insulin and Pdx1 cells were detected in the differentiated cultures. Although the pattern of pancreatic markers expression in these cultures was comparable to that of a mouse transformed β-cell line (MIN-6) and human islets, the expression levels of insulin observed in the differentiated ES cell cultures were several orders of magnitude lower. This suggests that, although PTD-TFs may prove useful in studying the role of exogenous TFs in the differentiation of ES cells towards islets and other pancreatic lineages, the amount of insulin generated is well below that required for therapeutically useful cells

The stress of starvation: glucocorticoid restraint of beta cell development

Developmental insults during gestation, such as under-nutrition, are known to restrict the number of beta cells that form in the fetal pancreas and are maintained in adulthood, leading to increased risk of type 2 diabetes. There are now substantial data indicating that glucocorticoids mediate this effect of under-nutrition on beta cell mass and that even at physiological levels they restrain fetal beta cell development in utero. There are emerging clues that this occurs downstream of endocrine commitment by neurogenin 3 but prior to terminal beta cell differentiation. Deciphering the precise mechanism will be important as it might unveil new pathways by which to manipulate beta cell mass that could be exploited as novel therapies for patients with diabetes

Inappropriate stereotypical inferences? An adversarial collaboration in experimental ordinary language philosophy

This paper trials new experimental methods for the analysis of natural language reasoning and the (re)development of critical ordinary language philosophy in the wake of J.L. Austin. Philosophical arguments and thought experiments are strongly shaped by default pragmatic inferences, including stereotypical inferences. Austin suggested that contextually inappropriate stereotypical inferences are at the root of some philosophical paradoxes and problems, and that these can be resolved by exposing those verbal fallacies. This paper builds on recent efforts to empirically document inappropriate stereotypical inferences that may drive philosophical arguments. We demonstrate that previously employed questionnaire-based output measures do not suffice to exclude relevant confounds. We then report an experiment that combines reading time measurements with plausibility ratings. The study seeks to provide evidence of inappropriate stereotypical inferences from appearance verbs that have been suggested to lie at the root of the influential ‘argument from illusion’. Our findings support a diagnostic reconstruction of this argument. They provide the missing component for proof of concept for an experimental implementation of critical ordinary language philosophy that is in line with the ambitions of current ‘evidential’ experimental philosophy

Retinoic Acid Promotes the Generation of Pancreatic Endocrine Progenitor Cells and Their Further Differentiation into β-Cells

The identification of secreted factors that can selectively stimulate the generation of insulin producing β-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based β-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of β-cells during normal pancreatic development such putative factors may be identified. In the mouse, β-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of β-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when β-cells are generated. We also provide evidence that RA induces the generation of Ngn3+ endocrine progenitor cells and stimulates their further differentiation into β-cells by activating a program of cell differentiation that recapitulates the normal temporal program of β-cell differentiation