Antiviral Responses in Mouse Embryonic Stem Cells: Differential Development of Cellular Mechanisms in Type I Interferon Production and Response

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and functionality would be significantly compromised if the cells do not have competent immunity. The responses of mESCs to three types of live viruses, La Crosse virus, West Nile virus, and Sendai virus, were firstly investigated. The results demonstrated that mESCs were susceptible to the viral infections, but they were unable to express type I interferons (IFNα and IFNβ). The failure of mESCs to express IFNα/β was further demonstrated with polyIC (polyinosinic-polycytidylic acid), a synthetic viral dsRNA analog that strongly induced IFNα/β in 10T1/2 cells. The author conclude that the mechanisms that mediate type I IFN expression are deficient in mESCs. It will be further demonstrated that single stranded RNA and protein encoding mRNA induce strong IFN expression and cytotoxicity in fibroblasts and cancer epithelial cells, but none of these effects associated with antiviral responses was observed in ESCs. Therefore, ESCs are intrinsically deficient in antiviral responses; in particular, they do not have functional mechanisms to express type I IFN. Furthermore, the author found that mESCs can respond to type I IFNs and express IFN-stimulated genes as in differentiated fibroblasts. IFNβ and IFNω can protect mESCs from La Crosse virus-induced cell death and inhibit the replication of LACV and West Nile Virus. In summary, these findings illustrated that the cellular mechanisms for production of and response to type I IFN are not equally developed in mESCs; they are deficient in type I IFN expression but have functional mechanisms that respond to and mediate the antiviral effects of type I IFN

Transient Inhibition of Cell Proliferation does not Compromise Self-Renewal of Mouse Embryonic Stem Cells

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. (C) 2012 Elsevier Inc. All rights reserved

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development of Cellular Mechanisms In Type I Interferon Production and Response

We have recently reported that mouse embryonic stem cells (mESCs) are deficient in expressing type I interferons (IFNs) in response to viral infection and synthetic viral RNA analogs (Wang, R., Wang, J., Paul, A. M., Acharya, D., Bai, F., Huang, F., and Guo, Y. L. (2013) J. Biol. Chem. 288, 15926–15936). Here, we report that mESCs are able to respond to type I IFNs, express IFN-stimulated genes, and mediate the antiviral effect of type I IFNs against La Crosse virus and chikungunya virus. The major signaling components in the IFN pathway are expressed in mESCs. Therefore, the basic molecular mechanisms that mediate the effects of type I IFNs are functional in mESCs; however, these mechanisms may not yet be fully developed as mESCs express lower levels of IFN-stimulated genes and display weaker antiviral activity in response to type I IFNs when compared with fibroblasts. Further analysis demonstrated that type I IFNs do not affect the stem cell state of mESCs. We conclude that mESCs are deficient in type I IFN expression, but they can respond to and mediate the cellular effects of type I IFNs. These findings represent unique and uncharacterized properties of mESCs and are important for understanding innate immunity development and ESC physiology

Mouse Embryonic Stem Cells Are Deficient in Type I Interferon Expression in Response to Viral Infections and Double-Stranded RNA

Embryonic stem cells (ESCs) are considered to be a promising cell source for regenerative medicine because of their unlimited capacity for self-renewal and differentiation. However, little is known about the innate immunity in ESCs and ESC-derived cells. We investigated the responses of mESCs to three types of live viruses; La Crosse virus (LACV), West Nile virus (WNV), and Sendai virus (SeV). Our results demonstrated mESCs were susceptible to viral infection, but they were unable to express type I interferons (IFNα and IFNβ,IFNα/β which differ from fibroblasts (10T1/2 cells) that robustly express IFNα/β upon viral infections. The failure of mESCs to express IFNα/β was further demonstrated by treatment with polyIC (polyinosinic-polycytidylic), a synthetic viral dsRNA analog that strongly induced IFNα/β in 10T1/2 cells. Although polyIC transiently inhibited the transcription of pluripotency markers, the stem cell morphology was not significantly affected. However, polyIC can induce dsRNA-activated protein kinase (PKR) in mESCs and this activation resulted in a strong inhibition of cell proliferation. We conclude that the cytosolic receptor PKR is functional, but the mechanisms that mediate type I IFN expression are deficient in mESCs. This conclusion is further supported by the findings that the major viral RNA receptors are either expressed at very low levels (TLR3 and MDA5) or may not be active (RIG-I) in mESCs

Field-effect transistors made from solution-grown two-dimensional tellurene

The reliable production of two-dimensional crystals is essential for the development of new technologies based on 2D materials. However, current synthesis methods suffer from a variety of drawbacks, including limitations in crystal size and stability. Here, we report the fabrication of large-area, high-quality 2D tellurium (tellurene) using a substrate-free solution process. Our approach can create crystals with a process-tunable thickness, from monolayer to tens of nanometres, and with lateral sizes of up to 100 um. The chiral-chain van der Waals structure of tellurene gives rise to strong in-plane anisotropic properties and large thickness dependent shifts in Raman vibrational modes, which is not observed in other 2D layered materials. We also fabricate tellurene field-effect transistors, which exhibit air-stable performance at room temperature for over two months, on off ratios on the order of 106 and field-effect mobilities of around 700 cm2 per Vs. Furthermore, by scaling down the channel length and integrating with high-k dielectrics, transistors with a significant on-state current density of 1 A mm-1 are demonstrated

Ultrafast Photoinduced Band Splitting and Carrier Dynamics in Chiral Tellurium Nanosheets

Trigonal tellurium (Te) is a chiral semiconductor that lacks both mirror and inversion symmetries, resulting in complex band structures with Weyl crossings and unique spin textures. Detailed time-resolved polarized reflectance spectroscopy is used to investigate its band structure and carrier dynamics. The polarized transient spectra reveal optical transitions between the uppermost spin-split H4 and H5 and the degenerate H6 valence bands (VB) and the lowest degenerate H6 conduction band (CB) as well as a higher energy transition at the L-point. Surprisingly, the degeneracy of the H6 CB (a proposed Weyl node) is lifted and the spin-split VB gap is reduced upon photoexcitation before relaxing to equilibrium as the carriers decay. Using ab initio density functional theory (DFT) calculations we conclude that the dynamic band structure is caused by a photoinduced shear strain in the Te film that breaks the screw symmetry of the crystal. The band-edge anisotropy is also reflected in the hot carrier decay rate, which is a factor of two slower along c-axis than perpendicular to it. The majority of photoexcited carriers near the band-edge are seen to recombine within 30 ps while higher lying transitions observed near 1.2 eV appear to have substantially longer lifetimes, potentially due to contributions of intervalley processes in the recombination rate. These new findings shed light on the strong correlation between photoinduced carriers and electronic structure in anisotropic crystals, which opens a potential pathway for designing novel Te-based devices that take advantage of the topological structures as well as strong spin-related properties.Comment: 42 pages, 13 figure

Hybrid Nanomanufacturing of Wearable Devices for Self-Powered Human-Integrated Sensor Systems

Electronics has become an inseparable part of our daily lives, stressing the supply of electrical power at anytime and anywhere. Besides reducing power consumption, increasing the energy density of the power supply component, and developing a sustainable power system that provides power by harvesting energy from the ambient environment are two solutions to address this challenge. To this end, my research goal is to transform advanced manufacturing through innovating designer functional nanomaterials for societally-pervasive areas including health monitoring, energy harvesting, human-machine interaction, and internet-of-things. Piezoelectric and triboelectric effects can convert mechanical energy to electricity, which enables the design of devices to utilize energy generated from the human body. The functional nanomaterials with such unique properties could be rationally synthesized and fabricated as sustainable power sources or self-powered systems. In this dissertation, two kinds of devices have been developed, the nanogenerator to covert mechanical energy from human body to electricity and the self-powered sensor. First, A series of biomaterial and biocompatible materials derived wearable energy harvesting devices were invented by systematically engineering the chemical and surface structures. Second, a versatile platform was developed for the monolithic integration of liquid-solid heterojunction devices through the hybrid manufacturing of bottom-up growth of 2D ZnO piezoelectric nanostructures on additively printed liquid metal electrodes. This new class of wearable devices are conformable to human skins and can sustainably perform non-invasive physiological functions, e.g. detection of pulses and vocal vibration, by harvesting the operation power from the human body. Besides, the controllable manufacturing of functional nanocrystals and their energy-related applications are also included. This dissertation is expected to have a positive impact and immediate relevance to many societally pervasive areas, e.g. energy and environment, biomedical electronics, and human-machine interface

Cultural prorogation in mainland China: a case study of BL culture

Boys‘love (BL) is originated from the Japanese comics. The phrase ―”boy‘s love” first appeared as a proper noun in the comics at an approximate time of 1966 in Japan. Most BL comics depicted hopeless love of boys. Then, the 1990s saw the emergence of new type of BL comics, namely 耽美 (Tanbi). Tanbi is a Japanese word, it can be attributed the same meaning as aestheticism. Tanbi comics showed a perfect scene to audiences within beautiful boys’ love, pleasure stories also end up with a comedy. The boys‘ love or nature love between boys is different from the circle of gay. BL is a kind of emotion always can only be seen in literary output due to its strict conditions. BL ought to be explained like this, a beautiful boy is falling love with somebody else, by coincidence, it is a beautiful boy. BL is more like a Platonic love, BL always give a picture of spiritual experiences of boys‘love but fewer sex. In other word, BL is just a kind of comic form. The researchers in Japanese comics always concentrated on its social influences, characteristics, conditions, etc. There is scarce any research touching on the comic forms. BL comics are a special component of the comics, and this form demonstrates a series of phenomenon in sociology. With an informal research, BL comics is now turning into a common fashionable comic form among the Asia regions. However, with great exchanges with other areas, there also exists a large number of BL comic fans in Mainland China, and most of them are young ladies. Given this background, BL is treated as an exclusive form to the young ladies, and it largely reflects values and tastes of these ladies. The findings of this thesis might provide insights into a desire understanding males and an expectation of a fathfully lover. Undeniably, Japanese people attain amazing achievements in many fields, the success of circulating BL products is one of them. To some extent, researching the circulation and consumption patterns of BL comics may reveal the great achievement of Japan in culture transmission.published_or_final_versionModern Languages and CulturesMasterMaster of Philosoph