BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo

At E4.0 the inner cell mass of the mouse blastocyst consists of a core of embryonic ectoderm cells surrounded by an outer layer of primitive (extraembryonic) endoderm, which subsequently gives rise to both visceral endoderm and parietal endoderm. Shortly after blastocyst implantation, the solid mass of ectoderm cells is converted by a process known as cavitation into a pseudostratified columnar epithelium surrounding a central cavity. We have previously used two cell lines, which form embryoid bodies that do (PSA1) or do not (S2) cavitate, as an in vitro model system for studying the mechanism of cavitation in the early embryo. We provided evidence that cavitation is the result of both programmed cell death and selective cell survival, and that the process depends on signals from visceral endoderm (Coucouvanis, E. and Martin, G. R. (1995) Cell 83, 279-287). Here we show that Bmp2 and Bmp4 are expressed in PSA1 embryoid bodies and embryos at the stages when visceral endoderm differentiation and cavitation are occurring, and that blocking BMP signaling via expression of a transgene encoding a dominant negative mutant form of BMP receptor IB inhibits expression of the visceral endoderm marker, Hnf4, and prevents cavitation in PSA1 embryoid bodies. Furthermore, we show that addition of BMP protein to cultures of S2 embryoid bodies induces expression of Hnf4 and other visceral endoderm markers and also cavitation. Taken together, these data indicate that BMP signaling is both capable of promoting, and required for differentiation of, visceral endoderm and cavitation of embryoid bodies. Based on these and other data, we propose a model for the role of BMP signaling during peri-implantation stages of mouse embryo development.     

Is leptin sensitivity the link between smoking cessation and weight gain?

We performed a case-control study to investigate the association of the poor metaboliser genotype of the cytochrome P450 2D6 gene with Parkinson's disease (PD). Genotyping was determined by the polymerase chain reaction followed by digestion with restriction enzymes. The poor metaboliser genotype was more frequent in 112 patients with PD than in 206 matched controls (odds ratio 1.7, 95% CI: 0.94-2.45). A meta-analysis of these results together with ten other published studies gave a pooled odds ratio for the poor metaboliser genotype of 1.47 (95% CI: 1.18-1.96, P=0.01). Thus, the poor metaboliser genotype has a small but highly significant association with PD which would be easily missed in small studies. Research now should focus on the mechanism of this association.     

Improving thermal performance of the roof enclosure of heavy construction buildings

High heat flux through the enclosures of heavy building constructions during summer and winter seasons is of great concern with respect to energy-related economics and environmental issues. This paper demonstrates the importance of quantitative evaluation of enclosure design and proves the potential for substantial energy savings by minor alterations of conventional roof designs. These modifications include adding insulation layer(s), removing construction details and obstructing fluid flow within the attic cavity by partial or full vertical partition within the cavity. The CFD approach adopted for this purpose is based on a numerical study of steady, conjugate natural convection in the cavity of an attic of heavy construction buildings. Because of the flow characteristics, laminar and turbulent models were employed for summer and winter day boundary conditions, respectively. Steady state results based on the finite-volume method were obtained for Rayleigh number in the range 10⁸–10¹⁰. Representative results illustrating the effects of the proposed design modifications on the local and total Nusselt numbers at the indoor surfaces are presented and discussed for summer and winter day boundary conditions. The results show that considerable energy saving may be achieved via relatively simple design changes. It is also shown that adding an insulation layer does not necessarily translate into energy conservation, and that eliminating a minor design detail might have significant rewards in terms of energy savings.