Myeloid-Derived Suppressor Cells Impair Alveolar Macrophages through PD-1 Receptor Ligation during Pneumocystis Pneumonia

Myeloid-derived suppressor cells (MDSCs) were recently found to accumulate in the lungs during Pneumocystis pneumonia (PcP). Adoptive transfer of these cells caused lung damage in recipient mice, suggesting that MDSC accumulation is a mechanism of pathogenesis in PcP. In this study, the phagocytic activity of alveolar macrophages (AMs) was found to decrease by 40% when they were incubated with MDSCs from Pneumocystis-infected mice compared to those incubated with Gr-1+ cells from the bone marrow of uninfected mice. The expression of the PU.1 gene in AMs incubated with MDSCs also was decreased. This PU.1 downregulation was due mainly to decreased histone 3 acetylation and increased DNA methylation caused by MDSCs. MDSCs were found to express high levels of PD-L1, and alveolar macrophages (AMs) were found to express high levels of PD-1 during PcP. Furthermore, PD-1 expression in AMs from uninfected mice was increased by 18-fold when they were incubated with MDSCs compared to those incubated with Gr-1+ cells from the bone marrow of uninfected mice. The adverse effects of MDSCs on AMs were diminished when the MDSCs were pretreated with anti-PD-L1 antibody, suggesting that MDSCs disable AMs through PD-1/PD-L1 ligation during PcP

Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4+ cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11blow CD11chigh alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP

Research on Wavelet Based Autofocus Evaluation in Micro-vision

AbstractThis paper presents the construction of two kinds of focusing measure operators defined in wavelet domain. One mechanism is that the Discrete Wavelet Transform (DWT) coefficients in high frequency subbands of in-focused image are higher than those of defocused one. The other mechanism is that the autocorrelation of an in-focused image filtered through Continuous Wavelet Transform (CWT) gives a sharper profile than blurred one does. Wavelet base, scaling factor and form to get the sum of high frequency energy are the key factors in constructing the operator. Two new focus measure operators are defined through the autofocusing experiments on the micro-vision system of the workcell for micro-alignment. The performances of two operators can be quantificationally evaluated through the comparison with two spatial domain operators Brenner Function (BF) and Squared Gradient Function (SGF). The focus resolution of the optimized DWT-based operators is 14% higher than that of BF and its computational cost is 52% approximately lower than BF's. The focus resolution of the optimized CWT-based operators is 41% lower than that of SGF whereas its computational cost is approximately 36% lower than SGF's. It shows that the wavelet based autofocus measure functions can be practically used in micro-vision applications

Repression of btuB gene transcription in Escherichia coli by the GadX protein

<p>Abstract</p> <p>Background</p> <p>BtuB (B twelve uptake) is an outer membrane protein of <it>Escherichia coli</it>, it serves as a receptor for cobalamines uptake or bactericidal toxin entry. A decrease in the production of the BtuB protein would cause <it>E. coli </it>to become resistant to colicins. The production of BtuB has been shown to be regulated at the post-transcriptional level. The secondary structure switch of 5' untranslated region of <it>butB </it>and the intracellular concentration of adenosylcobalamin (Ado-Cbl) would affect the translation efficiency and RNA stability of <it>btuB</it>. The transcriptional regulation of <it>btuB </it>expression is still unclear.</p> <p>Results</p> <p>To determine whether the <it>btuB </it>gene is also transcriptionally controlled by trans-acting factors, a genomic library was screened for clones that enable <it>E. coli </it>to grow in the presence of colicin E7, and a plasmid carrying <it>gadX </it>and <it>gadY </it>genes was isolated. The <it>lacZ </it>reporter gene assay revealed that these two genes decreased the <it>btuB </it>promoter activity by approximately 50%, and the production of the BtuB protein was reduced by approximately 90% in the presence of a plasmid carrying both <it>gadX </it>and <it>gadY </it>genes in <it>E. coli </it>as determined by Western blotting. Results of electrophoretic mobility assay and DNase I footprinting indicated that the GadX protein binds to the 5' untranslated region of the <it>btuB </it>gene. Since <it>gadX </it>and <it>gadY </it>genes are more highly expressed under acidic conditions, the transcriptional level of <it>btuB </it>in cells cultured in pH 7.4 or pH 5.5 medium was examined by quantitative real-time PCR to investigate the effect of GadX. The results showed the transcription of <it>gadX </it>with 1.4-fold increase but the level of <it>btuB </it>was reduced to 57%.</p> <p>Conclusions</p> <p>Through biological and biochemical analysis, we have demonstrated the GadX can directly interact with <it>btuB </it>promoter and affect the expression of <it>btuB</it>. In conclusion, this study provides the first evidence that the expression of <it>btuB </it>gene is transcriptionally repressed by the acid responsive genes <it>gadX </it>and <it>gadY</it>.</p

Enhanced surface acceleration of fast electrons by using sub-wavelength grating targets

Surface acceleration of fast electrons in intense laser-plasma interaction is improved by using sub-wavelength grating targets. The fast electron beam emitted along the target surface was enhanced by more than three times relative to that by using planar target. The total number of the fast electrons ejected from the front side of target was also increased by about one time. The method to enhance the surface acceleration of fast electron is effective for various targets with sub-wavelength structured surface, and can be applied widely in the cone-guided fast ignition, energetic ion acceleration, plasma device, and other high energy density physics experiments.Comment: 14 pages, 4figure