Inhibition of yes-associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model.

Yes-associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030-BrM3(K-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 mutation) cells (P < .05). H2030-BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61 compared to parental H2030 cells (P < .05). Inhibition of YAP by short hairpin RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA expression in downstream genes CTGF and CYR61 in H2030-BrM3 cells (P < .05). In addition, inhibiting YAP by YAP shRNA significantly decreased migration and invasion abilities of H2030-BrM3 cells (P < .05). We are first to show that mice inoculated with YAP shRNA-transfected H2030-BrM3 cells had significantly decreased metastatic tumour burden and survived longer than control mice (P < .05). Collectively, our results suggest that YAP plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP by shRNA suppresses H2030-BrM3 cell brain metastasis in a murine model

Effects of matrine on collagen proliferation and TNF-α, TGF-β1 and CTGF in atrial tissues of dogs with persistent atrial fibrillation

目的 探讨苦参碱对犬心房颤动（房颤）心房肌组织中胶原合成以及肿瘤坏死因子（tumor necrosis factor alpha,TNF-α）、转化生长因子（transforming growth factor-β1，TGF-β1）和结缔组织生长因子（connective Tissue Growth Factor，CTGF）表达变化的影响。方法 健康比格犬10只采用快速右心室起搏造房颤模型，随机分成房颤组和房颤+苦参碱组各5只。采用天狼星红染色，计算胶原容积分数（collagen volume fraction，CVF）以测定纤维化程度；采用免疫组织化学法检测右心房TNF-α、TGF-β1和CTGF的蛋白表达情况；用逆转录-聚合酶链反应（RT-PCR）技术检测TNF-α、TGF-β1和CTGF的mRNA水平表达情况。结果 与房颤组相比，房颤+苦参碱组纤维化程度降低，CVF明显下降（P＜0.05），TNF-α、TGF-β1和CTGF蛋白表达水平下降，且TNF-α和TGF-β1的mRNA表达水平显著下降（P＜0.05，P＜0.01）。结论 苦参碱可能通过抑制TNF-α、TGF-β1和CTGF的表达，抑制房颤心房肌胶原合成，改善心房组织纤维化程度。Objective:To study the effects of matrine (mat) on collagen synthesis and expression of tumor necrosis factoralpha (TNF-α), and transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in atrial tissues of dogs with persistent atrial fibrillation (AF). Methods : Ten healthy beagle dogs were randomly divided into two groups: AF group (n=5) and AF/Mat group (n=5), using right ventricular pacing to establish AF model. The collagen volume fraction (CVF) in atrial tissue were detected by sirius red staining to determine the level of fabrication. The level of TNF-α, TGF-β1 and CTGF were detected by immunohisto-chemistry. The mRNA expression level of TNF-α, TGF-β1 and CTGF were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results:  Compared with the AF group, the fabriation level of AF/Mat was decreased obviously (P<0.05), the expression levels of TNF-α, TGF-β1 and CTGF were decreased, and the mRNA expression level were decreased significantly in atrial tissues (P<0.05 and P<0.01). Conclusion: Matrine may inhibits fabrosis in atrial tissues through inhibition collagen proliferation and expression of TNF-α, TGF-β1 and CTGF

A Google Earth-based surveillance system for schistosomiasis japonica implemented in the lower reaches of the Yangtze River, China

<p>Abstract</p> <p>Background</p> <p>Due to the success of the national schistosomiasis control programme in China, transmission has been sufficiently reduced in many areas to severely limit identification of areas at risk by conventional snail surveys only. In this study, we imported Google Earth technology and a Global Positioning System (GPS) into the monitoring system for schistosomiasis surveillance of the banks of the Yangtze River in Jiangsu Province, China.</p> <p>Methods</p> <p>A total of 45 sites were selected and the risk was assessed monthly by water exposure of sentinel mice at these sites from May to September in 2009 and 2010. The results were assembled and broadcast via the Google Earth platform.</p> <p>Results</p> <p>The intensity of schistosomiasis transmission showed peaks of risk in June and September of 2009, while there was only one small peak in June in 2010 as the number of detected positive transmission sites dropped dramatically that year thanks to improved mollusciciding. River ports were found to be areas of particular risk, but ferry terminals and other centres of river-related activities were also problematic.</p> <p>Conclusions</p> <p>The results confirm that the surveillance system can be rapidly updated and easily maintained, which proves the Google Earth approach to be a user-friendly, inexpensive warning system for schistosomiasis risk.</p

Dendritic cell subsets dynamics and cytokine production in SIVmac239-infected Chinese rhesus macaques

BACKGROUND: Several studies have demonstrated that SIV infection progresses more slowly to experimental AIDS in Chinese rhesus macaques (Ch Rhs) than in Indian rhesus macaques (Ind Rhs). Here we investigated the dynamic and functional changes in dendritic cell (DC) subsets in SIVmac239-infected Ch Rhs. RESULTS: The numbers of both mDC and pDC strongly fluctuated but were not significantly changed during the acute and chronic phases of infection. However, the concentration of both poly (I:C)-induced IL-12 and HSV-1-induced IFN-α significantly increased in the acute phase of infection but returned to normal levels at the chronic phase of infection. The peak of IFN-α emerged earlier than that of IL-12, and it had a significantly positive correlation with IL-12, which indicated that IFN-α may initiate the immune activation. We also found that only the concentration of IFN-α was positively correlated with CD4+ T-cell counts, but it was negatively correlated with viral load. CONCLUSION: High levels of IFN-α in the early stage of infection may contribute to effective control of virus replication, and normal levels of IFN-α during chronic infection may help Ch Rhs resist the disease progression. The change in DC subsets dynamics and cytokine production may help further our understanding of why Ch Rhs are able to live longer without progressing to an AIDS-like illness

Repression of tyrosine hydroxylase is responsible for the sex-linked chocolate mutation of the silkworm, \u3cem\u3eBombyx mori\u3c/em\u3e

Pigmentation patterning has long interested biologists, integrating topics in ecology, development, genetics, and physiology. Wild-type neonatal larvae of the silkworm, Bombyx mori, are completely black. By contrast, the epidermis and head of larvae of the homozygous recessive sex-linked chocolate (sch) mutant are reddish brown. When incubated at 30 °C, mutants with the sch allele fail to hatch; moreover, homozygous mutants carrying the allele sch lethal (schl) do not hatch even at room temperature (25 °C). By positional cloning, we narrowed a region containing sch to 239,622 bp on chromosome 1 using 4,501 backcross (BC1) individuals. Based on expression analyses, the best sch candidate gene was shown to be tyrosine hydroxylase (BmTh). BmTh coding sequences were identical among sch, schl, and wild-type. However, in sch the ∼70-kb sequence was replaced with ∼4.6 kb of a Tc1-mariner type transposon located ∼6 kb upstream of BmTh, and in schl, a large fragment of an L1Bm retrotransposon was inserted just in front of the transcription start site of BmTh. In both cases, we observed a drastic reduction of BmTh expression. Use of RNAi with BmTh prevented pigmentation and hatching, and feeding of a tyrosine hydroxylase inhibitor also suppressed larval pigmentation in the wild-type strain, pnd+ and in a pS (black-striped) heterozygote. Feeding L-dopa to sch neonate larvae rescued the mutant phenotype from chocolate to black. Our results indicate the BmTh gene is responsible for the sch mutation, which plays an important role in melanin synthesis producing neonatal larval color

Three-Dimensional Flat Bands and Dirac Cones in a Pyrochlore Superconductor

Emergent phases often appear when the electronic kinetic energy is comparable to the Coulomb interactions. One approach to seek material systems as hosts of such emergent phases is to realize localization of electronic wavefunctions due to the geometric frustration inherent in the crystal structure, resulting in flat electronic bands. Recently, such efforts have found a wide range of exotic phases in the two-dimensional kagome lattice, including magnetic order, time-reversal symmetry breaking charge order, nematicity, and superconductivity. However, the interlayer coupling of the kagome layers disrupts the destructive interference needed to completely quench the kinetic energy. Here we experimentally demonstrate that an interwoven kagome network--a pyrochlore lattice--can host a three dimensional (3D) localization of electron wavefunctions. In particular, through a combination of angle-resolved photoemission spectroscopy, fundamental lattice model and density functional theory (DFT) calculations, we present the novel electronic structure of a pyrochlore superconductor, CeRu$_2$. We find striking flat bands with bandwidths smaller than 0.03 eV in all directions--an order of magnitude smaller than that of kagome systems. We further find 3D gapless Dirac cones predicted originally by theory in the diamond lattice space group with nonsymmorphic symmetry. Our work establishes the pyrochlore structure as a promising lattice platform to realize and tune novel emergent phases intertwining topology and many-body interactions.Comment: 12 pages, 3 figure