Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Adult human endometrial derived stem cells (HEDSC), a readily obtainable type of mesenchymal stem‐like cell, were used to generate dopaminergic cells and for transplantation. Cells expressing CD90, platelet derived growth factor (PDGF)‐Rβ and CD146 but not CD45 or CD31 were differentiated in vitro into dopaminergic neurons that exhibited axon projections, pyramidal cell bodies and dendritic projections that recapitulate synapse formation; these cells also expressed the neural marker nestin and tyrosine hydroxylase, the rate‐limiting enzyme in dopamine synthesis. Whole cell patch clamp recording identified G‐protein coupled inwardly rectifying potassium current 2 channels characteristic of central neurons. A 1‐methyl 4‐phenyl 1,2,3,6‐tetrahydro pyridine induced animal model of PD was used to demonstrate the ability of labelled HEDSC to engraft, migrate to the site of lesion, differentiate in vivo and significantly increase striatal dopamine and dopamine metabolite concentrations. HEDSC are a highly inducible source of allogenic stem cells that rescue dopamine concentrations in an immunocompetent PD mouse model.     

A combined A431 cell membrane chromatography and online high performance liquid chromatography/mass spectrometry method for screening compounds from total alkaloid of Radix Caulophylli acting on the human EGFR

We have developed an online analytical method that combines A431 cell membrane chromatography (A431/CMC) with high performance liquid chromatography and mass spectrometry (LC/MS) for identifying active components from Radix Caulophylli acting on human EGFR. Retention fractions on A431/CMC model were captured onto an enrichment column and the components were directly analyzed by combining a 10-port column switcher with an LC/MS system for separation and preliminary identification. Using Sorafenib tosylate as a positive control, taspine and caulophine from Radix Caulophylli were identified as the active molecules which could act on the EGFR. This A431/CMC-online-LC/MS method can be applied for screening active components acting on EGFR from traditional Chinese medicines exemplified by Radix Caulophylli and will be of great utility in drug discovery using natural medicinal herbs as a source of novel compounds.     

Young but not relatively old retrotransposons are preferentially located in gene‐rich euchromatic regions in tomato (Solanum lycopersicum) plants

Long terminal repeat (LTR) retrotransposons are the major DNA components of flowering plants. They are generally enriched in pericentromeric heterochromatin regions of their host genomes, which could result from the preferential insertion of LTR retrotransposons and the low effectiveness of purifying selection in these regions. To estimate the relative importance of the actions of these two factors on their distribution pattern, the LTR retrotransposons in Solanum lycopersicum (tomato) plants were characterized at the genome level, and then the distribution of young elements was compared with that of relatively old elements. The current data show that old elements are mainly located in recombination‐suppressed heterochromatin regions, and that young elements are preferentially located in the gene‐rich euchromatic regions. Further analysis showed a negative correlation between the insertion time of LTR retrotransposons and the recombination rate. The data also showed there to be more solo LTRs in genic regions than in intergenic regions or in regions close to genes. These observations indicate that, unlike in many other plant genomes, the current LTR retrotransposons in tomatoes have a tendency to be preferentially located into euchromatic regions, probably caused by their severe suppression of activities in heterochromatic regions. These elements are apt to be maintained in heterochromatin regions, probably as a consequence of the pericentromeric effect in tomatoes. These results also indicate that local recombination rates and intensities of purifying selection in different genomic regions are largely responsible for structural variation and non‐random distribution of LTR retrotransposons in tomato plants.     

FBXW7 suppresses epithelial‐mesenchymal transition and chemo‐resistance of non‐small‐cell lung cancer cells by targeting snai1 for ubiquitin‐dependent degradation

Objectives

FBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin‐mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear.

Materials and Methods

Immunohistochemical staining and qRT‐PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour‐adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere‐formation assays. Immunofluorescence and co‐immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW7.

Results

We detected the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW7 expression tend to have both poorer 5‐year survival outcomes, and shorter disease‐free survival, comparing to those with higher FBXW7 levels. Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo‐sensitivity and inhibiting Epithelial‐mesenchymal Transition (EMT) progress. Results further showed that FBXW7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC, which could be partially abrogated by restoring Snai1 expression.

Conclusions

FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC

     

Antigenicity and immunogenicity of SARS-CoV S protein receptor-binding domain stably expressed in CHO cells

The receptor-binding domain (RBD) of SARS coronavirus (SARS-CoV) spike (S) protein contains multiple conformation-dependent epitopes that induce neutralizing antibody responses. Here we used CHO-K1 cells to establish a cell line for stable expression of a 193-mer (residues 318-510) RBD (RBD193-CHO) and determined its antigenicity and immunogenicity. We found that RBD193-CHO reacted strongly with a panel of six monoclonal antibodies recognizing various conformational and linear epitopes in RBD, suggesting that this recombinant protein maintains intact conformation and good antigenicity. Immunization of mice with RBD193-CHO resulted in induction of high titers of RBD-specific neutralizing antibodies and potent IL-4-expressing T cell responses. RBD193-CHO induced immunity that protected a majority of the vaccinated mice from SARS-CoV challenge. These results suggest that the recombinant RBD produced in an established stable cell line maintains strong immunogenicity with high potential for use as an effective and economic subunit SARS vaccine.     

Nonlocal Immunized Mid-Infrared Magnetic Hot Spots in Graphene Junctions

Magnetic hot spots, which implies confinements and enhancements of magnetic fields, are demonstrated in graphene junctions (GJs) in the mid-infrared range. The appearance of magnetic hot spots in GJs comes from the conduction currents in the junction. In further, the extinction resonance peaks suffer blue shift, along with the increases in the magnetic fields inside junction area, when the junction width reduces. In opposite to the circumstances for electric field enhancements, neither magnetic field enhancements nor resonance frequency of GJs is perturbed by the intrinsic nonlocal electronic response of graphene. Such nonlocality immunized magnetic enhancement could be explained by the polarization dependent property of nonlocal effect.     

A functional genomics approach to dissect the mode of action of the Stagonospora nodorum effector protein SnToxA in wheat

In this study, proteomics and metabolomics were used to study the wheat response to exposure to the SnToxA effector protein secreted by the fungal pathogen Stagonospora nodorum during infection. Ninety-one different acidic and basic proteins and 101 metabolites were differentially abundant when comparing SnToxA- and control-treated wheat leaves during a 72-h time course. Proteins involved in photosynthesis were observed to increase marginally initially after exposure, before decreasing rapidly and significantly. Proteins and metabolites associated with the detoxification of reactive oxygen species in the chloroplast were also differentially abundant during SnToxA exposure, implying that the disruption of photosynthesis causes the rapid accumulation of chloroplastic reactive oxygen species. Metabolite profiling revealed major metabolic perturbations in central carbon metabolism, evidenced by significant increases in tricarboxylic acid (TCA) cycle intermediates, suggestive of an attempt by the plant to generate ATP and reducing equivalents in response to the collapse of photosynthesis caused by SnToxA. This was supported by the observation that the TCA cycle enzyme malate dehydrogenase was up-regulated in response to SnToxA. The infiltration of SnToxA also resulted in a significant increase in abundance of many pathogenicity-related proteins, even in the absence of the pathogen or other pathogen-associated molecular patterns. This approach highlights the complementary nature of proteomics and metabolomics in studying effector-host interactions, and provides further support for the hypothesis that necrotrophic pathogens, such as S. nodorum, appear to exploit existing host cell death mechanisms to promote pathogen growth and cause disease.     

用PO4细胞为靶细胞检测人血清中Epstein-Barr病毒IgA/MA抗体以诊断鼻咽癌

近年来,常用未经丙酮固定的、由丁酸和巴豆油激活的B95-8细胞或P3HR-1细胞为靶细胞,检测人血清中EB病毒IgA/MA抗体以早期诊断鼻咽癌,效果良好。但由于B95-8细胞含有多种EB病毒抗原,不能用丙酮固定,需多次离心沉淀,在浮悬状态下检测,技术比较复杂。     

双尾蚜属的种类与地理分布

双尾蚜属Diuraphis Aizenberg全世界记录13种,主要分布在古北界和新北界。根据种类丰富度和特有种成分,欧亚大陆的欧洲和中亚为该属蚜虫的现代第一分布中心,北美为第二分布中心。本文提供了该属所有13个种的分种检索表。双尾蚜属蚜虫在中国共有7种,主要分布在蒙新区。它们是：麦双尾蚜Diuraphis noxia (Mordvilko), 害冰麦双尾蚜D. nociva Zhang et Liang,冰草麦蚜D. (Holcaphis) agropyronophaga Zhang, 披碱草蚜D. (Holcaphis) elymophila Zhang, 西方麦蚜D. (Holcaphis) frequens (Walker), 雀麦蚜D. (Holcaphis) bromicola Hille Ris Lambers和绒毛草蚜D. (Holcaphis) holci (Hille Ris Lambers)。对中国种类进行了简要描述。