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Production of the Cancer-Preventive Glucoraphanin in Tobacco

Molecular Plant 2010年第4期3卷 751-759页

作者： Michael Dalgaard Mikkelsen Carl Erik Olsen barbara ann halkier University of Copenhagen Faculty of Life Sciences Department of Plant Biology Plant Biochemistry Laboratory VKR Research Centre for Pro-Active Plants 40 Thorvaldsensvej DK-1871 Frederiksberg C Copenhagen Denmark University of Copenhagen Faculty of Life Sciences Department of Basic Sciences and Environment/Bioorganic Chemistry 40 Thorvaldsensvej DK-1871 Frederiksberg C Copenhagen Denmark

Epidemiological studies have demonstrated reduced risk of developing cancer upon consumption of diets rich in cruciferous vegetables. This chemoprevention has been largely attributed to the presence of the natural products glu- cosinolates, particularly the methionine-derived glucoraphanin from broccoli. Improved nutrition by functional foods or health-promoting dietary supplements is an attractive means for prevention of lifestyle-based diseases. Towards this goal, we have engineered the glucoraphanin pathway into tobacco. First, we engineered elongation of the side chain of methionine to produce the key intermediate dihomo-methionine. This process is catalyzed through two cycles in a chain-elongation pathway that takes place partly in the cytosol and partly in the chloroplast. Second, by coupling the five enzymes of the chain-elongation pathway to eight enzymes of the glucosinolate pathway, we show production of glucoraphanin together with other glucosinolates derived from chain-elongated isoleucine and/or leucine. The conver- sion of methionine to glucoraphanin is obtained via 14 intermediates. Demonstrating the production of the high-value glucoraphanin in a heterologous host has great potential in the food and medicinal industry as a means to generate a stable, rich source of glucoraphanin for the benefit of human health.

关键词： Compartmentation secondary metabolism/natural products Agrobacterium Arabidopsis tobacco glucosinolates metabolic engineering.

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Biotechnological approaches in glucosinolate production

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Journal of Integrative Plant Biology 2018年第12期60卷 1231-1248页

作者： annette Petersen Cuiwei Wang Christoph Crocoll barbara ann halkier DynaMo Center Copenhagen Plant Science Centre Department of Plant and Environmental Sciences University of Copenhagen

Glucosinolates(GLSs) are sulfur-rich, amino acid-derived defense compounds characteristic of the Brassicales order. In the past, GLSs were mostly known as anti-nutritional factors in fodder, biopesticides in agriculture, and flavors in condiments such as mustard. However, in recent times, GLSs have received increased attention as promoters of human *** has spurred intensive research towards generating rich sources of health-promoting GLSs. We provide a comprehensive overview of the biotechnologica approaches applied to reach this goal. This includes optimization of GLS production and composition in native, GLS-producing plants, including hairy root and cell cultures thereof, as well as synthetic biology approaches in heterologous hosts, such as tobacco and the microbial organisms Escherichia coli and Saccharomyces cerevisiae. The progress using these different approaches is discussed.

关键词： GLS Biotechnological approaches in glucosinolate production

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GTR-Mediated Radial Import Directs Accumulation of Defensive Glucosinolates to Sulfur-Rich Cells in the Phloem Cap of Arabidopsis Inflorescence Stem

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Molecular Plant 2019年第11期12卷 1474-1484页

作者： Deyang Xu Pascal Hunziker Olga Koroleva Andreas Blennow Christoph Crocoll Alexander Schulz Hussam Hassan Nour-Eldin barbara ann halkier DynaMo Center Department of Plant and Environmental SciencesFaculty of ScienceUniversity of Copenhagen1871 Frederiksberg CDenmark Lonza Biologies Pic 228 Bath RoadSlough SL14DXUK Section for Plant Glycobiology Department of Plant and Environmental SciencesFaculty of ScienceUniversity of Copenhagen1871 Frederiksberg CDenmark

In the phloem cap region o i Arabidopsis plants,sulfur-rich cells(S-cells)accumulate>100 mM glucosinolates(GLS),but are biosynthetically *** source and route of S-cell-bound GLS remain *** this study,using single-cell sampling and scanning electron microscopy with energy-dispersive X-ray analysis we show that two GLS importers,NPF2.10/GTR1 and NPF2.11/GTR2,are critical for GLS accumulation in S-cells,although they are not localized in the *** of GLS levels in S-cells in multiple combinations of homo-and heterografts o lg t r l gtr2,biosynthetic null mutant and wild-type plants indicate that S-cells accumulate GLS via symplasmic connections either directly from neighboring biosynthetic cells or indirectly to non-neighboring cells expressing GTR1/*** sources and transport routes exist for different types of GLS,and vary depending on the position of S-cells in the inflorescence *** on these findings,we propose a model illustrating the GLS transport routes either directly from biosynthetic cells or via GTR-mediated import from apoplastic space radially into a symplasmic domain,wherein the S-cells are the ultimate ***,we observed accumulation of the cyanogenic glucoside defensive compounds in high-turgor cells in the phloem cap of Lotus japonicus,suggesting that storage of defensive compounds in high-turgor cells may be a general mechanism for chemical protection of the phloem cap.

关键词： Arabidopsis glucosinolate S-cell phloem cap xylem symplasmic transport

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The Glucosinolate Biosynthetic Gene A OP2 Mediates Feed-back Regulation of Jasmonic Acid Signaling in Arabidopsis

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Molecular Plant 2015年第8期8卷 1201-1212页

作者： Meike Burow Susanna Atwell Marta Francisco Rachel E. Kerwin barbara A. halkier Daniel J. Kliebenstein DynaMo Center of Excellence Department of Plant and Environmental Sciences Faculty of Science University of Copenhagen Thorvaldsensvej 40 1871Frederiksberg C Denmark Copenhagen Plant Science Centre Department of Plant and Environmental Sciences Faculty of Science University of Copenhagen Thorvaldsensvej 40 1871Frederiksberg C Denmark Department of Plant Sciences University of California at Davis Davis CA 95616 USA Mision Biologica de Galicia (MBG-CSIC) PO Box 28 36080 Pontevedra Spain

Survival in changing and challenging environments requires an organism to efficiently obtain and use its resources. Due to their sessile nature, it is particularly critical for plants to dynamically optimize their meta- bolism. In plant primary metabolism, metabolic fine-tuning involves feed-back mechanisms whereby the output of a pathway controls its input to generate a precise and robust response to environmental changes. By contrast, few studies have addressed the potential for feed-back regulation of secondary metabolism. In Arabidopsis, accumulation of the defense compounds glucosinolates has previously been linked to genetic variation in the glucosinolate biosynthetic gene AOP2. AOP2 expression can increase the transcript levels of two known regulators （MYB28 and MYB29） of the pathway, suggesting thatAOP2 plays a role in positive feed-back regulation controlling glucosinolate biosynthesis. We generated mutants affecting AOP2, MYB28/29, or both. Transcriptome analysis of these mutants identified a so far unrecognized link between AOP2 and jasmonic acid （JA） signaling independent of MYB28 and MYB29. Thus, AOP2 is part of a regulatory feed-back loop linking glucosinolate biosynthesis and JA signaling and thereby allows the glucosinolate pathway to influence JA sensitivity. The discovery of this regulatory feed-back loop provides insight into how plants optimize the use of resources for defensive metabolites.

关键词： feed-back regulation jasmonates JA signaling glucosinolates Arabidopsis

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Predicting ecological regime shift under climate change： New modelling techniques and potential of molecular-based approaches

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Current Zoology 2013年第3期59卷 403-417页

作者： Richard STAFFORD V. anne SMITH Dirk HUSMEIER Thomas GRIMA barbara-ann GUINN School of Applied Sciences Boumemouth University BH12 5BB UK School of Biology University of St Andrews St Andrews KY 16 9ST UK School of Mathematics and Statistics University of Glasgow G 12 8QW UK Department of Life Sciences University of Bedfordshire LU1 3JU UK

Ecological regime shift is the rapid transition from one stable community structure to another, often ecologically infe- rior, stable community. Such regime shifts are especially common in shallow marine communities, such as the transition of kelp forests to algal turfs that harbour far lower biodiversity. Stable regimes in communities are a result of balanced interactions be- tween species, and predicting new regimes therefore requires an evaluation of new species interactions, as well as the resilience of the ＇stable＇ position. While computational optimisation techniques can predict new potential regimes, predicting the most likely community state of the various options produced is currently educated guess work. In this study we integrate a stable regime op- timisation approach with a Bayesian network used to infer prior knowledge of the likely stress of climate change （or, in practice, any other disturbance） on each component species of a representative rocky shore community model. Combining the results, by calculating the product of the match between resilient computational predictions and the posterior probabilities of the Bayesian network, gives a refined set of model predictors, and demonstrates the use of the process in determining community changes, as might occur through processes such as climate change. To inform Bayesian priors, we conduct a review of molecular approaches applied to the analysis of the transcriptome of rocky shore organisms, and show how such an approach could be linked to meas- ureable stress variables in the field. Hence species-specific microarrays could be designed as biomarkers of in situ stress, and used to inform predictive modelling approaches such as those described here.

关键词： Regime shift Phase shift Altemative stable state Intertidal Food web Resilience

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Influence of rangeland protection and seasonal grazing on aboveground vegetation,forage quality and weight gain of small ruminants–a study in Thar Desert,Pakistan

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Journal of Mountain Science 2023年第2期20卷 403-414页

作者： ISLAM Muhammad RAZZAQ Abdul HASSAN Sawsan ZUBAIR Muhammad KALROO Muhammad Waseem KHAN Attaullah GUL Shamim AHMAD Sarfraz RISCHKOWSKY barbara ann LOUHAICHI Mounir International Center for Agricultural Research in Dry Areas(ICARDA) South AsiaIslamabad 44050Pakistan Animal Science Division Pakistan Agricultural Research CouncilIslamabad 44050Pakistan International Center for Agricultural Research in Dry Areas(ICARDA) Amman 11185Jordan Department of Forestry and Range Management Bahauddin Zakariya UniversityMultan 66000Pakistan PARC-Arid Zone Research Institute Umerkot 69100Pakistan Department of Botany University of BalochistanQuetta 87300Pakistan Department of Natural Resource Sciences McGill UniversityQuebec H9X3V9Canada Natural Resource Division Pakistan Agricultural Research CouncilIslamabad 44050Pakistan International Center for Agricultural Research in Dry Areas(ICARDA) SSAILRI campusAddis Ababa 5689Ethiopia International Center for Agricultural Research in Dry Areas(ICARDA) Tunis 1004Tunisia

The Thar Desert,Sindh,Pakistan is characterized by low ***,economy is based on agriculture,livestock and mining,nevertheless,livestock graze freely on public and private *** aim of this research was to determine biomass production and to evaluate the effects of continuous and seasonal grazing on protected and unprotected plots.A 45 ha protected rangeland area of Hurrabad in the Umerkot Thar desert was selected and divided into three blocks of 15 ha *** of the same size were also established in unprotected *** data for vegetation biomass,canopy cover,forage nutrients and weight gain of animals in two seasons(spring and summer)was collected from both protected and unprotected *** results showed that biomass significantly increased in summer in both ***,the biomass values in protected sites were significantly ***,the vegetation cover also seemed to increase in summer in both protected(90.7%±0.29%)and unprotected sites(39.2%±0.09%).The foliar concentrations of all nutrients varied significantly with *** average final live-weight gain for does on the protected grazing sites during the 42-day period in spring and the 96 days after the monsoon was almost double that of does grazing on the unprotected site during 2016 and 2017(P<0.05).The study concludes that the protection of grazing lands during certain periods can lead to better production of vegetation and livestock and improve range conditions.

关键词： Rangeland productivity Seasonal grazing Stocking rate Thar Desert Vegetation quality

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Molecular Epidemiology of Nontuberculous Mycobacteria in a German CF Center and Clinical Course of NTM Positive Patients

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Open Journal of Medical Microbiology 2013年第1期3卷 39-47页

作者： Carolin Kroner barbara Ganster Matthias Kappler ann-Christin Grimmelt Bernd H.Belohradsky Michael Hogardt Gudrun Laniado Michael Meissner Soren Schubert Matthias Griese Paediatric Pneumology Dr.von Hauner Children’s HospitalLudwig-Maximilians-UniversityMunichGermany Institute for Clinical Chemistry Molecular DiagnosticsMedical Microbiology and Hygiene DepartmentLudwigshafen General HospitalLudwigshafenGermany Institute for Medical Microbiology and Infection Control University HospitalJohann-Wolfgang-Goethe-UniversityFrankfurt/MainGermany Max von Pettenkofer Institute of Hygiene and Medical Microbiology Ludwig-Maximilians-UniversityMunichGermany

Goal of this study was to analyse the clinical course of cystic fibrosis (CF) patients with nontuberculous mycobacteria (NTM) in their respiratory secretions and to investigate the molecular epidemiology of the most prevalent NTM species by multilocus sequence analysis (MLSA). The respiratory specimen and the clinical parameters forced expiratory volume in one second (FEV1), body-mass-index (BMI), erythrocyte sedimentation rate (ESR) 1 h and immunoglobulin G (IgG) of 357 CF patients, 0 - 52.4 years, mean FEV1 2009 81.5% pred were analysed between 1998 and 2010. In 13 patients NTM were detected. 12 of 13 patients carried M. abscessus, for one patient the NTM species was not characterized. 4 patients carried a second NTM species (M. avium, M. chelonae (2x), M. intracellulare). 6 patients exhibited a significant decline in FEV1, however changes in BMI, IgG and ESR were discordant. Molecular genotyping of M. abscessus isolates revealed a unique MLSA pattern in 6 patients. 2 patients harboured identical strains, and one patient a closely related strain. Whether the presence of identical strains is attributed to the acquisition of NTM clones from common environmental sources or to patient-to-patient transmission cannot be definitely clarified. Although cross-in- fection of the three patients with identical/closely related strains in the present cohort is highly unlikely, we recommend strict hygiene measures for all CF patients harbouring NTM.

关键词： Mycobacteria Nontuberculous Mycobacterium abscessus Cystic Fibrosis Molecular Epidemiology Multilocus Sequence Analysis(MLSA) Interferon Gamma

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Vocational education of female entrepreneurs in China:A multitheoretical and multidimensional analysis of successful businesswomen’s everyday lives

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Frontiers of Education in China 2015年第3期10卷 498-500页

作者： barbara SCHULTE Lund University

This book is about vocational education,but also about possibilities of non-/informal education;it is about China,but also about a specific ethnic minority group(the Dongxiang),which is,among other things,characterized by Islamic faith;it is about entrepreneurship,and more specifically about successful female business women;it is about these women’s everyday lives;and,if that was not enough,the author calls her analysis also“multitheoretical.”Any reader who might now be expecting a weighty tome will be surprised to notice that Mary ann Maslak’s book contains a running text of a little more than 80 *** might have been foreknown,this brevity compromises both scope and depth of an analysis that otherwise could have been insightful and multi-faceted.

关键词： education everyday analysis

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Renal cell carcinoma escapes NK cell-mediated immune surveillance through the downregulation of DNAM-1

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Cancer Communications 2023年第7期43卷 855-859页

作者： Veronika Kremer Shi Yong Neo Yaxuan Liu Yi Chen Arnika Kathleen Wagner Ying Yang Ziqing Chen Christina Seitz Nicholas Patrick Tobin Maarten Alexander Ligtenberg Evren Alici Xinsong Chen Felix Haglund barbara Seliger Ulrika Harmenberg Eugenia Colón ann-Helén Scherman Plogell Lisa Lei Liu Andreas Lundqvist Department of Oncology-Pathology Karolinska InstitutetStockholmSweden Singapore Immunology Network Agency for ScienceTechnology and ResearchSingaporeSingapore Department of Medicine Columbia University Irving Medical CenterNew YorkUSA Department of Medicine Huddinge Karolinska InstitutetStockholmSweden Department of Molecular Biology Princeton UniversityNew JerseyUSA Institute of Environmental Medicine Karolinska InstitutetStockholmSweden Department of Molecular Oncology The Netherlands Cancer InstituteAmsterdamNetherlands Institute for Medical Immunology Martin-Luther University Halle-WittenbergHalleGermany Institute of Translational Immunology Medical School Theodor FontaneBrandenburg an der Havel14770and Fraunhofer Institute for Cell Therapy and ImmunologyLeipzigGermany Department ofWomen’s and Children’s Health Karolinska Institutet and S:t Göran’s Hospital-UnilabsStockholmSweden Department of Urology Stockholm South General HospitalStockholmSweden

Dear Editor,The activating receptor DNAX accessory molecule-1(DNAM-1)plays an important role in T and natural killer(NK)cell-mediated cytotoxicity via the interaction with its ligands poliovirus receptor(PVR,CD155)and Nectin-2(CD112).Compared with peripheral blood NK cells,tumor-infiltrating NK cells show reduced expression of DNAM-1 across several solid tumors,including ovarian and breast cancer resulting in impaired NK cell *** studies reported an inverse correlation between DNAM-1 expression and its ligands in leukemic blasts and ovarian cancer[1].

关键词： impaired cancer killer

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Proteasome inhibitor for cancer treatment

Proteasome inhibitor for cancer treatment

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： HuanjieYang~1,Q Ping Dou~2 1.Department of life science and engineering,Harbin Institute of Technology 2.barbara ann Karmanos Cancer Institute,Wayne State University

The ubiquitin-proteasome degradation pathway plays an essential role in multiple cellular processes,including cell cycle progression,proliferation,apoptosis and *** vitro,in vivo and clinical studies suggest the potential use of proteasome inhibitors as novel anticancer *** the current study,we are providing experimental evidence for that celastrol isolated from traditional Chinese medicine potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome and human prostate cancer cellular 26S *** of the proteasome activity by celastrol in PC-3 (androgen receptor- or AR-negative) or LNCaP(AR-positive) cells results in the accumulation of ubiquitinated proteins and three natural proteasome substrates(I B-,Bax,and p27),accompanied by suppression of AR protein expression(in LNCaP cells) and induction of *** with celastrol resulted in tumor growth inhibition in prostate cancer xenografts,associated with suppression of the proteasomal activity and induction of apoptosis in *** results show that celastrol is a natural proteasome inhibitor that has a great potential for cancer *** computational modeling,it was predicted that the ketone carbons of celastrol might interact with the catalytic site of chymotryptic subunit of the ***,the reduced form of celastrol had significantly decreased proteasome inhibitory and apoptosis-inducing activities,suggesting that the ketone structure was an active site of *** further investigated the role of AR on cell death modulation in response to proteasome inhibition and found that proteasome inhibitor induced significantly higher caspase-3 activation in parental PC-3 cells compared to PC3-AR cells that stably overexpressed wild type ***-treatment of proteasome inhibitor and the AR antagonist Casodex caused significant decrease in AR expression associated with an increase in caspase-3 activity in both LNCaP and PC3-AR cel

关键词： Proteasome Cancer Apoptosis Androgen Receptor

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