An in vitro stem cell model of human epiblast and yolk sac interaction.

Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.

Exposure to Intermittent Noise Exacerbates the Cardiovascular Response of Wistar-Kyoto Rats to Ozone Inhalation and Arrhythmogenic Challenge.

Noise has become a prevalent public health problem across the world. Although there is a significant amount of data demonstrating the harmful effects of noise on the body, very little is known about how it impacts subsequent responses to other environmental stressors like air pollution, which tend to colocalize in urban centers. Therefore, this study was conducted to determine the effect of intermittent noise on cardiovascular function and subsequent responses to ozone (O3). Male Wistar-Kyoto rats implanted with radiotelemeters to non-invasively measure heart rate (HR) and blood pressure (BP), and assess heart rate variability (HRV) and baroreflex sensitivity (BRS) were kept in the quiet or exposed to intermittent white noise (85-90 dB) for one week and then exposed to either O3 (0.8 ppm) or filtered air. Left ventricular function and arrhythmia sensitivity were measured 24 h after exposure. Intermittent noise caused an initial increase in HR and BP, which decreased significantly later in the regimen and coincided with an increase in HRV and BRS. Noise caused HR and BP to be significantly elevated early during O3 and lower at the end when compared to animals kept in the quiet while the increased HRV and BRS persisted during the 24 h after. Lastly, noise increased arrhythmogenesis and may predispose the heart to mechanical function changes after O3. This is the first study to demonstrate that intermittent noise worsens the cardiovascular response to inhaled O3. These effects may occur due to autonomic changes and dysregulation of homeostatic controls, which persist one day after exposure to noise. Hence, co-exposure to noise should be taken into account when assessing the health effects of urban air pollution.

Computational studies on response and binding selectivity of fluorescence sensors.

Using a computational strategy based on density functional theory calculations, we successfully designed a fluorescent sensor for detecting Zn(2+) [J. Phys. Chem. B 2006, 110, 22991-22994]. In this work, we report our further studies on the computational design protocol for developing Photoinduced Electron Transfer (PET) fluorescence sensors. This protocol was applied to design a PET fluorescence sensor for Zn(2+) ions, which consists of anthracene as the fluorophore connected to pyridine as the receptor through dimethylethanamine as the linker. B3LYP and time-dependent B3LYP calculations were performed with the basis set 6-31G(d,p), 6-31+G(d,p), 6-311G(d,p), and 6-311+G(d,p). The calculated HOMO and LUMO energies of the fluorophore and receptor using all four basis sets show that the relative energy levels remain unchanged. This indicates that any of these basis sets can be used in calculating the relative molecular orbital (MO) energy levels. Furthermore, the relative MO energies of the independent fluorophore and receptor are not altered when they are linked together, which suggests that one can calculate the MO energies of these components separately and use them as the MO energies of the free sensor. These are promising outcomes for the computational design of sensors, though more case studies are needed to further confirm these conclusions. The binding selectivity studies indicate that the predicted sensor can be used for Zn(2+) even in the presence of the divalent cation, Ca(2+).