The amniote primitive streak is defined by epithelial cell intercalation before gastrulation

During gastrulation, a single epithelial cell layer, the ectoderm, generates two others: the mesoderm and the endoderm. In amniotes (birds and mammals), mesendoderm formation occurs through an axial midline structure, the primitive streak, the formation of which is preceded by massive 'polonaise' movements of ectoderm cells. The mechanisms controlling these processes are unknown. Here, using multi-photon time-lapse microscopy of chick (Gallus gallus) embryos, we reveal a medio-lateral cell intercalation confined to the ectodermal subdomain where the streak will later form. This intercalation event differs from the convergent extension movements of the mesoderm described in fish and amphibians (anamniotes): it occurs before gastrulation and within a tight columnar epithelium. Fibroblast growth factor from the extraembryonic endoderm (hypoblast, a cell layer unique to amniotes) directs the expression of Wnt planar-cell-polarity pathway components to the intercalation domain. Disruption of this Wnt pathway causes the mesendoderm to form peripherally, as in anamniotes. We propose that the amniote primitive streak evolved from the ancestral blastopore by acquisition of an additional medio-lateral intercalation event, preceding gastrulation and acting independently of mesendoderm formation to position the primitive streak at the midline.     

Embedding Quantum Mechanics into a Broader Noncontextual Theory

Scholars concerned with the foundations of quantum mechanics (QM) usually think that contextuality (hence nonobjectivity of physical properties, which implies numerous problems and paradoxes) is an unavoidable feature of QM which directly follows from the mathematical apparatus of QM. Based on some previous papers on this issue, we criticize this view and supply a new informal presentation of the extended semantic realism (ESR) model which embodies the formalism of QM into a broader mathematical formalism and reinterprets quantum probabilities as conditional on detection rather than absolute. Because of this reinterpretation a hidden variables theory can be constructed which justifies the assumptions introduced in the ESR model and proves its objectivity. When applied to special cases the ESR model settles long-standing conflicts (it reconciles Bell’s inequalities with QM), provides a general framework in which previous results obtained by other authors (as local interpretations of the GHZ experiment) are recovered and explained, and supports an interpretation of quantum logic which avoids the introduction of the problematic notion of quantum truth.     

Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.     

HIV/AIDS: modified stem cells in the spotlight

Since HIV/AIDS was first recognized in 1981, an urgent need has existed for the development of novel therapeutic strategies to treat the disease. Due to the current antiretroviral therapy not being curative, human stem cell-based therapeutic intervention has emerged as an approach for its treatment. Genetically modified hematopoietic stem cells (HSCs) possess the potential to self-renew, reconstitute the immune system with HIV-resistant cells, and thus control, or even eliminate, viral replication. However, HSCs may be difficult to isolate in sufficient number from HIV-infected individuals for transplantation and/or re-infusion of autologous HSCs preparations would also include some contaminating HIV-infected cells. Furthermore, since genetic modification of HSCs is not completely efficient, the risk of providing unprotected immune cells to become new targets for HIV to infect could contribute to continued immune system failure. Therefore, induced pluripotent stem cells (iPSCs) should be considered a new potential source of cells to be engineered for HIV resistance and subsequently differentiated into clonal anti-HIV HSCs or hematopoietic progeny for transplant. In this article, we provide an overview of the current possible cellular therapies for treating HIV/AIDS.     

Coexpression of two distinct muscle acetylcholine receptor alpha-subunits during development

The nicotinic acetylcholine receptor is a ligand-gated channel that mediates signalling at the vertebrate neuromuscular junction. It is a pentameric complex of four different subunits, assembled with a stoichiometry of alpha 2 beta gamma delta. Muscle-like alpha-subunits have been cloned from Torpedo, mouse, calf, rat, chicken, human and Xenopus, and only a single alpha-subunit complementary DNA from each species has been detected. We report here the cloning and characterization of a second muscle alpha-subunit cDNA from Xenopus, and show that this and a previously reported Xenopus alpha-subunit cDNA are encoded by distinct genes. The novel alpha-subunit reported here is expressed uniquely in oocytes; but both types of alpha-subunit are coexpressed throughout muscle development. This latter observation indicates that the expression of these two alpha-subunits is different from a previously reported developmental 'subunit-switch' mechanism used to generate channel diversity.