Correlation between the number of CpG dinucleotides in the indicated regions of primate lentiviral env genes and the infectious virus yield in the presence of ZAP. Symbols in all panels represent the average value obtained for one IMC from the indicated groups in five experiments. See the Fig. 2 legend for further detail. Download FIG S2, TIF file, 2.0 MB.
Effect of ZAP on HIV-1 RNA and protein expression. (A) Effect of ZAP on infectious HIV-1 yield (top) and the levels of viral env mRNA (bottom). Shown are mean values (SEM) from at least three experiments. Numbers in parentheses indicate the number of CpGs in the ZAPsen region of each tested HIV-1 strain. Asterisks indicate significant differences from the HIV-2 7312 control construct. (B) Viral protein expression in transfected HEK293T cells and virions in the presence or absence of ZAP. To examine the effect of ZAP on viral protein expression levels, HEK293T ZAP KO cells were cotransfected with the indicated HIV-1 IMCs and ZAP expression or control vector and analyzed as described in Materials and Methods. (C) Quantification of Env protein expression levels in the presence of ZAP. Asterisks indicate significant differences from the HIV-1 RHGA control construct. (D) Correlations between infectious virus yield in the presence of ZAP and env mRNA or Env protein expression levels. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
It has been previously shown that ZAP efficiently inhibits HIV-1 NHG constructs containing artificially high levels of CpG dinucleotides but not the parental wild-type virus (6). To map viral determinants of ZAP sensitivity, we overexpressed ZAP and found that at high levels it efficiently inhibits essentially all primary HIV-1 IMCs, although most of them were less susceptible to ZAP than the HIV-1 NHG strain (Fig. 2). The levels of ZAP expression in transiently transfected HEK293T cells were higher than those observed in primary CD4+ T cells and macrophages representing the major viral target cells in vivo. They are highly similar, however, to the levels of endogenous ZAP expression in HeLa and THP-1 cells (Fig. 7A). ZAP knockout almost invariantly increased infectious virus yield, particularly if the HIV-1 molecular clones contained relatively high numbers of CpGs in the ZAPsen region of the env gene. These results suggest that the observed differences in viral sensitivity to ZAP overexpression may be relevant for HIV-1 replication in primary viral target cells. Examination of HIV-1 sequences from individuals with known rates of clinical progression supports a role of the number of CpGs in the ZAPsen region of env in clinical progression to AIDS. Whether reduced sensitivity to ZAP or other effects of reduced CpG numbers are responsible for this link to disease progression has to be addressed in future studies.
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Abstract:The human body cannot store zinc reserves, so a deficiency can arise relatively quickly, e.g., through an improper diet. Severe zinc deficiency is rare, but mild deficiencies are common around the world. Many epidemiological studies have shown a relationship between the zinc content in the diet and the risk of cancer. The anti-cancer effect of zinc is most often associated with its antioxidant properties. However, this is just one of many possibilities, including the influence of zinc on the immune system, transcription factors, cell differentiation and proliferation, DNA and RNA synthesis and repair, enzyme activation or inhibition, the regulation of cellular signaling, and the stabilization of the cell structure and membranes. This study presents selected issues regarding the current knowledge of anti-cancer mechanisms involving this element.Keywords: zinc; immune system; cancer; defense mechanisms
In this work, we demonstrate multilayer semitransparent structures for producing transmissive colors with high-color-purity, angle-insensitivity, and high efficiency, based on a higher-order resonance suppression. Although employing a 3rd order F-P resonance leads to a narrowband transmission in a spectral curve of transmittance as compared to a fundamental F-P resonance for achieving the high-color-purity transmissive colors, a 5th order F-P resonance appears at a short wavelength regime when the 3rd order F-P resonance is utilized for color generation, which significantly degrade the color purity. To address this challenge, the structural color filters are designed to have an electric field intensity profile with a maximum value of the 5th order resonance but a minimum value of the 3rd order resonance at the center of the cavity so that only the 5th order resonance is significantly suppressed without affecting the 3rd order resonance by introducing a lossy medium in a middle of the cavity. This guarantees the high-color-purity transmission color generation without sacrificing the transmission efficiency. Besides, a resonant wavelength of the individual structural color filters remains almost constant in wavelength over a broad range of incident angles up to 60, due to a phase compensation by a dielectric overlay and a small refraction angle by a cavity material with a high index of refraction. Additionally, the structural color filters, fabricated on a flexible substrate, present insensitive performances against the number of a bending deformation and a bending radius. The present concept can be easily enabled by a simple deposition method, which can offer a key step toward the realization of the large-scale applications in a variety of research fields, including as e-paper display technologies, image sensors, flexible optoelectronic devices, and decorations.
(a) Positions of a resonant wavelength and (b) maximum values of a transmission efficiency of the fabricated transmissive structural color filters on a plastic substrate as a function of a radius of curvature. (c) Maximum values of the transmission efficiency of the blue structural color against the number of bending deformation tests. (d) Optical images of the fabricated transmissive structural color filters on the flexible substrate.
In summary, we have demonstrated flexible structural transmissive colors featuring wide angle, high efficiency, and high saturation, exploiting the 3rd order F-P resonance at resonant wavelengths with an efficient suppression of the 5th order F-P resonance at shorter wavelengths. The ultrathin light-absorbing layer is placed in the middle of the optical cavity, where the structural color filters show a maximum intensity of the electric field for the 5th order F-P resonance but a minimum intensity of the electric field for the 3rd order F-P resonance, thereby yielding a considerable suppression of only the 5th order F-P resonance and a significantly improved saturation without lowering the transmission efficiency. Moreover both high refractive index of the cavity medium and the phase compensating dielectric overlay allow the resonant wavelengths to remain almost constant for a wide angle of incidence up to 60. Furthermore, the optical properties of the flexible structural transmissive colors are found to be pretty insensitive to both the bending radius and the number of the bending deformation. The strategy described in this work could offer the distinct potentials to achieve diverse large-scale applications, such as flexible display devices, wearable electronics, imaging devices, decorations, and colored solar cells.
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We generated Zbtb46fl/fl and Zbtb46fl/flMx1-Cre mice. The deletion of Zbtb46 in Zbtb46fl/flMx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46fl/fl and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry.
The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46fl/fl littermates (Zbtb46fl/flvs. Zbtb46 cKO, HPC: 801,310 84,282 vs. 907,202 97,403, t = 0.82, P = 0.46; LSK: 86,895 7802 vs. 102,210 5025, t = 1.65, P = 0.17; HSC: 19,753 3116 vs. 17,608 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46fl/flMx1-Cre mice was similar to those from Zbtb46fl/fl control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation. 1e1e36bf2d