Direct observation of elemental fluctuation and oxygen octahedral distortion-dependent charge distribution in high entropy oxides

The enhanced compositional flexibility to incorporate multiple-principal cations in high entropy oxides (HEOs) offers the opportunity to expand boundaries for accessible compositions and unconventional properties in oxides. Attractive functionalities have been reported in some bulk HEOs, which are attributed to the long-range compositional homogeneity, lattice distortion, and local chemical bonding characteristics in materials. However, the intricate details of local composition fluctuation, metal-oxygen bond distortion and covalency are difficult to visualize experimentally, especially on the atomic scale. Here, we study the atomic structure-chemical bonding-property correlations in a series of perovskite-HEOs utilizing the recently developed four-dimensional scanning transmission electron microscopy techniques which enables to determine the structure, chemical bonding, electric field, and charge density on the atomic scale. The existence of compositional fluctuations along with significant composition-dependent distortion of metal-oxygen bonds is observed. Consequently, distinct variations of metal-oxygen bonding covalency are shown by the real-space charge-density distribution maps with sub-ångström resolution. The observed atomic features not only provide a realistic picture of the local physico-chemistry of chemically complex HEOs but can also be directly correlated to their distinctive magneto-electronic properties

FATS is a transcriptional target of p53 and associated with antitumor activity

Frequent mutations of p53 in human cancers exemplify its crucial role as a tumor suppressor transcription factor, and p21, a transcriptional target of p53, plays a central role in surveillance of cell-cycle checkpoints. Our previous study has shown that FATS stabilize p21 to preserve genome integrity. In this study we identified a novel transcript variant of FATS (GenBank: GQ499374) through screening a cDNA library from mouse testis, which uncovered the promoter region of mouse FATS. Mouse FATS was highly expressed in testis. The p53-responsive elements existed in proximal region of both mouse and human FATS promoters. Functional study indicated that the transcription of FATS gene was activated by p53, whereas such effect was abolished by site-directed mutagenesis in the p53-RE of FATS promoter. Furthermore, the expression of FATS increased upon DNA damage in a p53-dependent manner. FATS expression was silent or downregulated in human cancers, and overexpression of FATS suppressed tumorigenicity in vivo independently of p53. Our results reveal FATS as a p53-regulated gene to monitor genomic stability

Control of Domain Structures in Multiferroic Thin Films through Defect Engineering

Domain walls (DWs) have become an essential component in nanodevices based on ferroic thin films. The domain configuration and DW stability, however, are strongly dependent on the boundary conditions of thin films, which make it difficult to create complex ordered patterns of DWs. Here, it is shown that novel domain structures, that are otherwise unfavorable under the natural boundary conditions, can be realized by utilizing engineered nanosized structural defects as building blocks for reconfiguring DW patterns. It is directly observed that an array of charged defects, which are located within a monolayer thickness, can be intentionally introduced by slightly changing substrate temperature during the growth of multiferroic BiFeO3 thin films. These defects are strongly coupled to the domain structures in the pretemperatureâ change portion of the BiFeO3 film and can effectively change the configuration of newly grown domains due to the interaction between the polarization and the defects. Thus, two types of domain patterns are integrated into a single film without breaking the DW periodicity. The potential use of these defects for building complex patterns of conductive DWs is also demonstrated.Engineered structural defects are used as nanosized building blocks for configuring domainâ wall patterns in multiferroic BiFeO3 thin films. By utilizing the interaction between the polarization and the defects, two types of twinning domain structures are integrated into a single film without breaking the domainâ wall periodicity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146435/1/adma201802737-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146435/2/adma201802737_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146435/3/adma201802737.pd

Efficient gene editing in adult mouse livers via adenoviral delivery of CRISPR/Cas9

AbstractWe developed an adenovirus-based CRISPR/Cas9 system for gene editing in vivo. In the liver, we demonstrated that the system could reach the level of tissue-specific gene knockout, resulting in phenotypic changes. Given the wide spectrum of cell types susceptible to adenoviral infection, and the fact that adenoviral genome rarely integrates into its host cell genome, we believe the adenovirus-based CRISPR/Cas9 system will find applications in a variety of experimental settings

Probing the light harvesting and charge rectification of bismuth nanoparticles behind the promoted photoreactivity onto Bi/BiOCl catalyst by (in-situ) electron microscopy

State-of-the-art electron microscopy has enabled us to investigate microstructural details down to sub-subångström and milli-electron-volt resolution level. The enhanced photoreactivity over bismuth hybridized BiOCl catalyst (Bi/BiOCl) has been reported recently, however, the mechanistic understandings of this improved photoreactivity especially the optical behavior of bismuth nanoparticles (Bi NPs) are still obscured and in debate. The optical absorption features of Bi NPs and the charge transfer characteristic between bismuth and BiOCl have been considered as the major physicochemical origin for the promoted photoreactivity. Based on the advanced (in-situ) electron microscopy of monochromated electron energy loss spectroscopy in scanning transmission electron microscopy imaging mode (Mono-STEM-EELS) along with related theoretical investigations, in this work, we for the first time distinguished and explained the optical absorption originated from the localized surface plasmon resonances (LSPR) effect and direct band gap transition in an individual bismuth nanoparticle as well as transportation of photogenerated carriers at the interface of Bi/BiOCl. These findings could provide better understandings about the origin of the improved photoreactivity of various bismuth-hybridized photocatalysts

Trio-Based Deep Sequencing Reveals a Low Incidence of Off-Target Mutations in the Offspring of Genetically Edited Goats

Unintended off-target mutations induced by CRISPR/Cas9 nucleases may result in unwanted consequences, which will impede the efficient applicability of this technology for genetic improvement. We have recently edited the goat genome through CRISPR/Cas9 by targeting MSTN and FGF5, which increased muscle fiber diameter and hair fiber length, respectively. Using family trio-based sequencing that allow better discrimination of variant origins, we herein generated offspring from edited goats, and sequenced the members of four family trios (gene-edited goats and their offspring) to an average of ∼36.8× coverage. This data was to systematically examined for mutation profiles using a stringent pipeline that comprehensively analyzed the sequence data for de novo single nucleotide variants, indels, and structural variants from the genome. Our results revealed that the incidence of de novo mutations in the offspring was equivalent to normal populations. We further conducted RNA sequencing using muscle and skin tissues from the offspring and control animals, the differentially expressed genes (DEGs) were related to muscle fiber development in muscles, skin development, and immune responses in skin tissues. Furthermore, in contrast to recently reports of Cas9 triggered p53 expression alterations in cultured cells, we provide primary evidence to show that Cas9-mediated genetic modification does not induce apparent p53 expression changes in animal tissues. This work provides adequate molecular evidence to support the reliability of conducting Cas9-mediated genome editing in large animal models for biomedicine and agriculture

Cloning and Molecular Characterization of HSL and Its Expression Pattern in HPG Axis and Testis during Different Stages in Bactrian Camel

Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelusdromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction