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  • Metabolic engineering for the production of plant isoquinoline alkaloids

    分类: 生物学 >> 植物学 >> 植物生物化学、植物生物物理学 提交时间: 2016-05-04

    摘要: Several plant isoquinoline alkaloids (PIAs) possess powerful pharmaceutical and biotechnological properties. Thus, PIA metabolism and its fascinating molecules, including morphine, colchicine and galanthamine, have attracted the attention of both the industry and researchers involved in plant science, biochemistry, chemical bioengineering and medicine. Currently, access and availability of high-value PIAs [commercialized (e.g. galanthamine) or not (e.g. narciclasine)] is limited by low concentration in nature, lack of cultivation or geographic access, seasonal production and risk of overharvesting wild plant species. Nevertheless, most commercial PIAs are still extracted from plant sources. Efforts to improve the production of PIA have largely been impaired by the lack of knowledge on PIA metabolism. With the development and integration of next-generation sequencing technologies, high-throughput proteomics and metabolomics analyses and bioinformatics, systems biology was used to unravel metabolic pathways allowing the use of metabolic engineering and synthetic biology approaches to increase production of valuable PIAs. Metabolic engineering provides opportunity to overcome issues related to restricted availability, diversification and productivity of plant alkaloids. Engineered plant, plant cells and microbial cell cultures can act as biofactories by offering their metabolic machinery for the purpose of optimizing the conditions and increasing the productivity of a specific alkaloid. In this article, is presented an update on the production of PIA in engineered plant, plant cell cultures and heterologous micro-organisms.

  • Impacts of wind erosion and seasonal changes on soil carbon dioxide emission in southwestern Iran

    分类: 地球科学 >> 地球科学史 提交时间: 2020-10-20 合作期刊: 《干旱区科学》

    摘要: Wind erosion is one of the main drivers of soil loss in the world, which affects 20 million hectare land of Iran. Besides the soil loss, wind erosion contributes to carbon dioxide emission from the soil into the atmosphere. The objective of this study is to evaluate monthly and seasonal changes in carbon dioxide emission in four classes i.e., low, moderate, severe and very severe soil erosion and the interactions between air temperature and wind erosion in relation to carbon dioxide emission in the Bordekhun region, Boushehr Province, southwestern Iran. Wind erosion intensities were evaluated using IRIFR (Iran Research Institute of Forests and Ranges) model, in which four classes of soil erosion were identified. Afterward, we measured carbon dioxide emission on a monthly basis and for a period of one year using alkali traps in each class of soil erosion. Data on emission levels and erosion classes were analyzed as a factorial experiment in a completely randomized design with twelve replications in each treatment. The highest rate of emission occurred in July (4.490 g CO2/(m2•d)) in severely eroded lands and the least in January (0.086 g CO2/(m2•d)) in low eroded lands. Therefore, it is resulted that increasing erosion intensity causes an increase in soil carbon dioxide emission rate at severe erosion intensity. Moreover, the maximum amount of carbon dioxide emission happened in summer and the minimum in winter. Soil carbon dioxide emission was just related to air temperature without any relationship with soil moisture content; since changes of soil moisture in the wet and dry seasons were not high enough to affect soil microorganisms and respiration in dry areas. In general, there are complex and multiple relationships between various factors associated with soil erosion and carbon dioxide emission. Global warming causes events that lead to more erosion, which in turn increases greenhouse gas emission, and rising greenhouse gases will cause more global warming. The result of this study demonstrated the synergistic effect of wind erosion and global climate warming towards carbon dioxide emission into the atmosphere.

  • Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia

    分类: 生物学 >> 生物医药 提交时间: 2017-05-10

    摘要: To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro. ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor #1; (RAR#1;) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G1/G0 arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RAR#1; degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.

  • Quantifying the sequence-function relation in gene silencing by bacterial small RNAs

    分类: 物理学 >> 交叉学科物理及相关领域的科学与技术 提交时间: 2016-05-08

    摘要: Sequence-function relations for small RNA (sRNA)-mediated gene silencing were quantified for the sRNA RyhB and some of its mRNA targets in Escherichia coli. Numerous mutants of RyhB and its targets were generated and their in vivo functions characterized at various levels of target and RyhB expression. Although a core complementary region is required for repression by RyhB, variations in the complementary sequences of the core region gave rise to a continuum of repression strengths, correlated exponentially with the computed free energy of RyhB-target duplex formation. Moreover, sequence variations inthe linker region known to interact with the RNA chaperone Hfq also gave rise to a continuum of repression strengths, correlated exponentially with thecomputed energy cost of keeping the linker region open. These results support the applicability of the thermodynamic model in predicting sRNA-mRNA interaction and suggest that sequences at these locations may be used to fine-tune the degree of repression. Surprisingly, a truncated RyhB without the Hfq-binding region is found to repress multiple targets of the wild-type RyhB effectively, both in the presence and absence of Hfq, even though the former is required for the activity of wild-type RyhB itself. These findings challenge the commonly accepted model concerning the function of Hfq in gene silencing-bothin providing stability to the sRNAs and in catalyzing the target mRNAs to take on active conformations-and raise the intriguing question of why many endogenous sRNAs subject their functions to Hfq-dependences.

  • JIPB对标国际著名植物学期刊的卓越之路

    分类: 数字出版 >> 互联网期刊 提交时间: 2024-01-23

    摘要: 【目的】Journal of Integrative Plant Biology(以下简称JIPB)通过对标国际著名植物学期刊,探索追赶、超越发展的对策与举措,为我国加快国际一流科技期刊建设提供参考与借鉴。【方法】采用数据比较分析法和案例分析法。利用VOSviewer软件构建关键词共现网络图谱。通过与植物学领域国际著名期刊Journal of Experimental Botany(以下简称JXB)对标,分析JIPB与JXB的主要文献计量指标,包括期刊影响因子、总被引频次、国际论文比、期刊引文指标、作者分布、学科辐射范围、年发文量和顶尖论文方面的情况。【结果】JIPB 受中国科技期刊卓越行动计划(以下简称卓越计划)资助以来,通过采取由国内外一线权威科学家深度参与办刊、发表具有原始创新性的重大成果、建立专业的期刊管理体系、提供高效优质的出版服务等一系列举措追赶并部分超越JXB,建设成效显著。【结论】JIPB在卓越计划的资助下,以国际著名植物学期刊为标杆,不断提高学术水平和国际影响力,其国际化发展策略以及办刊实践是对建设卓越期刊的有益尝试,探索出了一条我国建设国际一流科技期刊的卓越之路。

  • Circulating Peptidome to Indicate the Tumor-resident Proteolysis

    分类: 生物学 >> 生物物理学 提交时间: 2016-05-12

    摘要: Tumor-resident proteases (TRPs) are regarded as informative biomarkers for staging cancer progression and evaluating therapeutic efficacy. Currently in the clinic, measurement of TRP is dependent on invasive biopsies, limiting their usefulness as monitoring tools. Here we identified circulating peptides naturally produced by TRPs, and evaluated their potential to monitor the efficacy of anti-tumor treatments. We established a mouse model for ovarian cancer development and treatment by orthotopic implantation of the human drug-resistant ovarian cancer cell line HeyA8-MDR, followed by porous silicon particle-or multistage vector (MSV) -enabled EphA2 siRNA therapy. Immunohistochemistry staining of tumor tissue revealed decreased expression of matrix metallopeptidase 9 (MMP-9) in mice exhibiting positive responses to MSV-EphA2 siRNA treatment. We demonstrated, via an ex vivo proteolysis assay, that C3f peptides can act as substrates of MMP-9, which cleaves C3f at L-1311-L-1312 into two peptides (SSATTFRL and LWENGNLLR). Importantly, we showed that these two C3f-derived fragments detected in serum were primarily generated by tumor-resident, but not blood-circulating, MMP-9. Our results suggested that the presence of the circulating fragments specially derived from the localized cleavage in tumor microenvironment can be used to evaluate therapeutic efficacy of anti-cancer treatment, assessed through a relatively noninvasive and user-friendly proteomics approach.

  • Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method

    分类: 生物学 >> 生物物理学 提交时间: 2016-05-12

    摘要: The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia), KK47 (low grade nonmuscle invasive bladder cancer, NMIBC), and YTS1 (metastatic bladder cancer) have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC) progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO) term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer.