Xin Zhang

With the emergence of clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) as one of the most promising new gene-editing techniques, scientists are now endeavoring to apply it to various domains. Among all the possible applications, gene editing in human embryos has received the most attention. Against this background, this article carries out a philosophical study on the ethical problems of human embryo gene editing or designing. Arguments against human embryo gene designing include that parents should be prohibited from deciding their children’s future; commodifying children should be prohibited; the natural reproductive process should not be disturbed; and human embryo gene designing might foster discrimination. Arguments for human embryo gene designing include that parents should have the freedom to design their own babies and this freedom should not be limited; designing babies can promote the happy life of the baby; and totally forbidding embryo gene editing would drive the practice underground, where it would be performed illegally. This article analyzes all of these arguments and points out that all of them have some flaws. In order to draw a thoughtful conclusion, we turn to Confucianism and find a new perspective to determine whether designing babies with CRISPR technology is ethically permissible.

Multi-focus image fusion means fusing a completely clear image with a set of images of the same scene and under the same imaging conditions with different focus points. In order to get a clear image that contains all relevant objects in an area, the multi-focus image fusion algorithm is proposed based on wavelet transform. Firstly, the multi-focus images were decomposed by wavelet transform. Secondly, the wavelet coefficients of the approximant and detail sub-images are fused respectively based on the fusion rule. Finally, the fused image was obtained by using the inverse wavelet transform. Among them, for the low-frequency and high-frequency coefficients, we present a fusion rule based on the weighted ratios and the weighted gradient with the improved edge detection operator. The experimental results illustrate that the proposed algorithm is effective for retaining the detailed images.

DNA base pairing has been used for many years to direct the arrangement of inorganic nanocrystals into small groupings and arrays with tailored optical and electrical properties. The control of DNA-mediated assembly depends crucially on a better understanding of three-dimensional structure of DNA-nanocrystal-hybridized building blocks. Existing techniques do not allow for structural determination of these flexible and heterogeneous samples. Here we report cryo-electron microscopy and negative-staining electron tomography approaches to image, and three-dimensionally reconstruct a single DNA-nanogold conjugate, an 84-bp double-stranded DNA with two 5-nm nanogold particles for potential substrates in plasmon-coupling experiments. By individual-particle electron tomography reconstruction, we obtain 14 density maps at ~ 2-nm resolution. Using these maps as constraints, we derive 14 conformations of dsDNA by molecular dynamics simulations. The conformational variation is consistent with that from liquid solution, suggesting that individual-particle electron tomography could be an expected approach to study DNA-assembling and flexible protein structure and dynamics.

Cholesteryl ester transfer protein mediates cholesteryl ester transfer from the atheroprotective high density lipoprotein cholesterol to the atherogenic low density lipoprotein cholesterol. In the past decade, this property has driven the development of CETP inhibitors, which have been evaluated in large scale clinical trials for treating cardiovascular diseases. Despite the pharmacological interest, little is known about the fundamental mechanism of CETP in CE transfer. Recent electron microscopy experiments have suggested a tunnel mechanism, and molecular dynamics simulations have shown that the flexible N-terminal distal end of CETP penetrates into the HDL surface and takes up a CE molecule through an open pore. However, it is not known whether a CE molecule can completely transfer through an entire CETP molecule. Here, we used all-atom molecular dynamics simulations to evaluate this possibility. The results showed that a hydrophobic tunnel inside CETP is sufficient to allow a CE molecule to completely transfer through the entire CETP within a predicted transfer time and at a rate comparable with those obtained through physiological measurements. Analyses of the detailed interactions revealed several residues that might be critical for CETP function, which may provide important clues for the effective development of CETP inhibitors and treatment of cardiovascular diseases.

Commonly used methods for determining protein structure, including X-ray crystallography and single-particle reconstruction, often provide a single and unique three-dimensional structure. However, in these methods, the protein dynamics and flexibility/fluctuation remain mostly unknown. Here, we utilized advances in electron tomography to study the antibody flexibility and fluctuation through structural determination of individual antibody particles rather than averaging multiple antibody particles together. Through individual-particle electron tomography 3D reconstruction from negatively-stained ET images, we obtained 120 ab-initio 3D density maps at an intermediate resolution from 120 individual IgG1 antibody particles. Using these maps as a constraint, we derived 120 conformations of the antibody via structural flexible docking of the crystal structure to these maps by targeted molecular dynamics simulations. Statistical analysis of the various conformations disclosed the antibody 3D conformational flexibility through the distribution of its domain distances and orientations. This blueprint approach, if extended to other flexible proteins, may serve as a useful methodology towards understanding protein dynamics and functions.

© 2015 Macmillan Publishers Limited All rights reserved. Genome-wide gene expression measurements have enabled comprehensive studies that integrate the changes of gene expression and phenotypic information to uncover their novel associations. Here we reported the association analysis between psychophysical phenotypes and genome-wide gene expression changes in human adaptation to one of the most extreme climates on Earth, the Antarctic Dome Argus. Dome A is the highest ice feature in Antarctica, and may be the coldest, driest and windiest location on earth. It is considered unapproachable due to its hostile environment. In 2007, a Chinese team of 17 male explorers made the expedition to Dome A for scientific investigation. Overall, 133 psychophysical phenotypes were recorded, and genome-wide gene expression profiles from the blood samples of the explorers were measured before their departure and upon their arrival at Dome A. We found that mood disturbances, including tension, depression, anger and fatigue, had a strong, positive, linear relationship with the level of a male sex hormone, testosterone, using the Pearson correlation coefficient analysis. We also demonstrated that significantly lowest-level Gene Ontology groups in changes of gene expression in blood cells with erythrocyte removal were consistent with the adaptation of the psychophysical characteristics. Interestingly, we discovered a list of genes that were strongly related to significant phenotypes using phenotype and gene expression PCC analysis. Importantly, among the 70 genes that were identified, most were significantly related to mood disturbances, where 42 genes have been reported in the literature mining, suggesting that the other 28 genes were likely novel genes involved in the mood disturbance mechanism. Taken together, our association analysis provides a reliable method to uncover novel genes and mechanisms related to phenotypes, although further studies are needed.