5,871 research outputs found

    The anomalous antiferromagnetic topological phase in pressurized SmB6

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    Antiferromagnetic materials, whose time-reversal symmetry is broken, can be classified into the Z2 topology if they respect some specific symmetry. Since the theoretical proposal, however, no materials have been found to host the antiferromagnetic topological (AFT) phase to date. Here, for the first time, we demonstrate that the topological Kondo insulator SmB6 can be an AFT system when pressurized to undergo an antiferromagnetic phase transition. In addition to propose the possible candidate for an AFT material, in this work we also illustrate the anomalous topological surface states of the AFT phase which has not been discussed before. Originating from the interplay between the topological properties and the antiferromagnetic surface magnetization, the topological surface states of the AFT phase behave differently as compared with those of a topological insulator. Besides, the AFT insulators are also found promising in the generation of tunable spin currents, which is an important application in spintronics

    GPER-induced signaling is essential for the survival of breast cancer stem cells.

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    G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

    Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein

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    Background: Though n-butanol has been proposed as a potential transportation biofuel, its toxicity oftencauses oxidative stress in the host microorganism and is considered one of the bottlenecks preventing itsefficient mass production.Results: To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengersfor reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT),mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed thegreatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, andnickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress.Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging butalso regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion proteincould contribute in an enhancement of the host microorganism’s growth rate.Conclusions: The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli wereexamined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein,OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These resultspresented indicate potential novel approaches for engineering stress tolerant microorganism strains

    TIME millimeter wave grating spectrometer

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    The Tomographic Ionized-carbon Mapping Experiment (TIME) utilizes grating spectrometers to achieve instantaneous wideband coverage with background-limited sensitivity. A unique approach is employed in which curved gratings are used in parallel plate waveguides to focus and diffract broadband light from feed horns toward detector arrays. TIME will measure singly ionized carbon fluctuations from 5 < z < 9 with an imaging spectrometer. 32 independent spectrometers are assembled into two stacks of 16, one per polarization. Each grating has 210 facets and provides a resolving power R of ~ 200 over the 186–324 GHz frequency range. The dispersed light is detected using 2-D arrays of transition edge sensor bolometers. The instrument is housed in a closed-cycle 4K–1K–300mK cryostat. The spectrometers and detectors are cooled using a dual-stage 250/300 mK refrigerator

    Toll-like receptor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy

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    BACKGROUND: Although cytotoxic T lymphocytes (CTLs) play a major role in eradicating cancer cells during immunotherapy, the cancer-associated immunosuppressive microenvironment often limits the success of such therapies. Therefore, the simultaneous induction of cancer-specific CTLs and reversal of the immunosuppressive tumor microenvironment may be more effectively achieved through a single therapeutic vaccine. A recombinant lipoprotein with intrinsic Toll-like receptor 2 (TLR2) agonist activity containing a mutant form of E7 (E7m) and a bacterial lipid moiety (rlipo-E7m) has been demonstrated to induce robust CTL responses against small tumors. This treatment in combination with other TLR agonists is able to eliminate large tumors. METHODS: Mouse bone marrow-derived dendritic cells (DCs) were employed to determine the synergistic production of pro-inflammatory cytokines upon combination of rlipo-E7m and other TLR agonists. Antigen-specific CTL responses were investigated using immunospots or in vivo cytolytic assays after immunization in mice. Mice bearing various tumor sizes were used to evaluate the anti-tumor effects of the formulation. Specific subpopulations of immunosuppressive cells in the tumor infiltrate were quantitatively determined by flow cytometry. RESULTS: We demonstrate that a TLR9 agonist (unmethylated CpG oligodeoxynucleotide, CpG ODN) enhances CTL responses and eradicates large tumors when combined with rlipo-E7m. Moreover, combined treatment with rlipo-E7m and CpG ODN effectively increases tumor infiltration by CTLs and reduces the numbers of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) in the tumor microenvironment. CONCLUSION: These findings suggest that the dramatic anti-tumor effects of the recombinant lipoprotein together with CpG ODN may reflect the amplification of CTL responses and the repression of the immunosuppressive environment. This promising approach could be applied for the development of additional therapeutic cancer vaccines
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