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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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Maize response to nitrogen and phosphorus starter fertilisation in mineral-fertilised or manured systems

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The Crop Journal 2023年第3期11卷 922-932页

作者： Michela Battisti barbara Moretti Massimo Blandino Carlo Grignani Laura Zavattaro Department of Agricultural Forest and Food SciencesUniversity of TurinLargo Braccini 2Grugliasco 10095TOItaly Department of Veterinary Sciences University of TurinLargo Braccini 2Grugliasco 10095TOItaly

Phosphorus(P)is an essential nutrient for maize production,but in temperate areas the P uptake during early growing stages can be limited due to low soil temperature,even though the soil was tested high in *** objective of this study was to assess the effects of nitrogen and phosphorous(NP)starter fertilisation during early growth stages and its carryover until maize harvest,in mineral-fertilised or manured systems.A field experiment was carried out in north-west Italy during the 2019 and 2020 growing *** trial compared sub-surface placement of NP(diammonium phosphate)or N alone(ammonium nitrate)in bands close to the maize seed furrows,in differing long-term(LT)fertilisation managements:two doses of urea(Min-L and Min-H),two doses of bovine slurry(Slu-L and Slu-H)or two doses of farmyard manure(Fym-L and Fym-H).The two rates,low(L)and high(H),corresponded to 170 and250 kg N ha^(-1)year^(-1) *** to N fertilisation,NP starter fertilisation improved early maize growth assessed by leaf area index(LAI)and shoot dry weight(SDW)in all *** effects differed between the two years(2019:LAI+63%,SDW+67%;2020:LAI+36%,SDW+38%),as 2019was cool during the first *** LAI and SDW values were confirmed at crop flowering in the mineral-fertilised systems *** shoot growth was enhanced by NP starter fertilisation,anthesis occurred 1 day earlier in all ***,a response to NP starter fertilisation at harvest was recorded in mineral-fertilised systems only(+1.3 and+3.2 t ha^(-1) in Min-L and Min-H,respectively).The uptake of P,used as a true indicator of soil nutrient availability,increased with increasing soil Olsen P until 39 mg kg^(-1).These results suggest that soil test thresholds should be revised for points above which P fertilisation should be suspended.

关键词： Long-term fertilisation Farmyard manure Bovine slurry Urea Diammonium phosphate

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A Reverse Dynamical Investigation of the Catastrophic Wood-Snow Avalanche of 18 January 2017 at Rigopiano, Gran Sasso National Park, Italy

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International Journal of Disaster Risk Science 2021年第1期12卷 40-55页

作者： barbara Frigo Perry Bartelt Bernardino Chiaia Igor Chiambretti Margherita Maggioni Department of Structural Building and Geotechnical Engineering-DISEGPolitecnico di Torino10129 TurinItaly WSL Institute for Snow and Avalanche Research SLF 7260 Davos DorfSwitzerland Associazione Interregionale di Coordinamento e documentazione per i problemi inerenti alla Neve e alle Valanghe–AINEVA 38122 TrentoItaly Dipartimento di Scienze Agrarie Universita`di TorinoForestali e Alimentari–DISAFA10095 GrugliascoTOItaly Centro Interdipartimentale sui Rischi Naturali in Ambiente Montano e Collinare–NatRisk 10095 GrugliascoTOItaly

On 18 January 2017 a catastrophic avalanche destroyed the Rigopiano Gran Sasso Resort&Wellness(Rigopiano Hotel)in the Gran Sasso National Park in Italy,with 40 people trapped and a death toll of *** article describes the location of the disaster and the general meteorological scenario,with field investigations to provide insight on the avalanche dynamics and its interaction with the hotel *** data gathered in situ suggest that the avalanche was a fluidized dry snow avalanche,which entrained a sligthtly warmer snow cover along the path and reached extremely long runout distances with braking effect from mountain *** avalanche that reached the Rigopiano area was a‘‘wood-snow’’avalanche—a mixture of snow and uprooted and crushed trees,rocks,and other *** were no direct eyewitnesses at the event,and a quick post-event survey used a numerical model to analyze the dynamics of the event to estimate the pressure,velocity,and direction of the natural flow and the causes for the destruction of the *** the magnitude and the damage caused by the event,the avalanche was at a high to very high intensity scale.

关键词： Avalanche flow velocity Avalanche impact pressure Forensic field investigation Italy Rigopiano disaster Wood-snow avalanche

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Collembola communities and soil conditions in forest plantations established in an intensively managed agricultural area

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Journal of Forestry Research 2021年第5期32卷 1819-1832页

作者： István Harta barbara Simon Szergej Vinogradov Dániel Winkler Institute of Environmental Science Szent István UniversityGödöllőHungary Institute of Methodology Szent István UniversityGödöllőHungary Institute of Wildlife Management and Vertebrate Zoology University of SopronSopronHungary

The challenges of a changing climate have directed greater attention to afforestation,but the effects of afforestation on soil fertility and soil biota have not been fully *** explore changes in the soil conditions in two 20-year-old forest plantations established in formerly intensively fertilized plots of agricultural land,we focused on the current developmental state of the sites that received the most fertilizer and evaluated soil properties and Collembola(springtails)*** oak(Quercus petraea)and black locust(Robinia pseudoacacia)that had been planted in the afforestation sites were assessed for differences between plantations of native and invasive *** adjacent reference associations,including forests and open habitats,were also analyzed and *** showed that the soils in the two afforested sites were similar in their properties and Collembola communities to those of the control cultivated forests,but differed from each other in pH,calcium,phosphorus,and ammonium *** available potassium and phosphorus contents in the soil of the sessile oak plantation were still high,while the soil organic matter content was adequate(SOM>2.0%)in both *** richness of Collembola ranged from 18 in the cultivated arable land to 43 in the relict *** a few species typical for forests(e.g.,Neanura muscorum,Isotomiella minor,Entomobrya muscorum)were detected in the young plantations,while species characteristic of open habitats(e.g.,Protaphorura campata,Lepidocyrtus cyaneus)occurred as *** more individuals and species of Collembola were present in the soil of young plantations than in arable fields,their community diversities were significantly lower compared to the control forest *** community diversity differed significantly also between the two plantation types(with native and non-native tree species).Mean abundance in the afforested sites was about 2.5 times higher than in the cultiv

关键词： Afforestation Diversity Fertilizers Soil fauna Soil properties Springtails

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Role of circulating tumor cell spheroids in drug resistance

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Cancer Drug Resistance 2019年第3期2卷 762-772页

作者： Gerhard Hamilton barbara Rath Department of Surgery Medical University of ViennaVienna A-1090Austria

Cancer cell spheroids are used for drug screening as these three-dimensional(3D)assemblies recapitulate tumors more realistic than the widely employed 2D in vitro *** drug diffusion and gradients of oxygen and nutrients in spheroids represent avascular tumor regions containing quiescent and hypoxic tumor cells with high drug *** tumor cells(CTCs)effect metastatic spread and are present in high numbers in malignant diseases such as small-cell lung cancer(SCLC)and in other cancer patients with high tumor *** are heterogeneous and only a small fraction of these cells survive in the circulation and cause distal *** may circulate as single cells but small CTC clusters or CTC spheroids have been detected in cancer patients and demonstrated to possess increased metastatic *** our lab we have obtained 9 permanent SCLC CTC cell lines(BHGc7,BHGc10,BHGc16,BHGc26,BHGc27,BHGc50,BHGc59,BHGc71,and UHGc5)of distinct patients exhibiting similar characteristics and spontaneous formation of large spheroids,termed *** aggregates were shown to exhibit high drug resistance compared to the corresponding single cell *** increased metastatic capability of small circulating tumor clusters/spheroids may be explained by their role as putative precursors of tumorospheres eventually trapped in *** drug penetration and the presence of hypoxic/quiescent cells can readily account for the global drug resistance of advanced SCLC which has resulted in clinical failure of a wide range of chemotherapeutics and low ***,we have detected such tumorospheres in non-small-cell lung cancer(NSCLC)patients progressing under EGFR-directed tyrosine kinase inhibitor therapy which had undergone NSCLC-SCLC transformation.

关键词： Cancer spheroid circulating tumor cells small cell lung cancer non-small-cell lung cancer transformation dormancy

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Difficulties in diagnosing angiomatoid fibrous histiocytoma of the head and neck region:A case report

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世界临床病例杂志 2023年第26期11卷 6252-6261页

作者： Adam Michcik Marta Bień barbara Wojciechowska Adam Polcyn Łukasz Garbacewicz Jacek Kowalski barbara Drogoszewska Department of Maxillofacial Surgery Medical University of GdańskGdańsk 80-214Poland Department of Pathomorphology Medical University of GdańskGdańsk 80-214Poland

BACKGROUND Angiomatoid fibrous histiocytoma(AFH)is a rare,slow-growing soft tissue *** appears mostly on the limbs and trunk in children and young *** biology of AFH remains unclear because of the small number of reported *** testing does not provide definitive *** has two clinical forms,that differ in terms of gene expression and clinical *** is important to inform the laboratory which specific gene testing is ***,we describe a case of rare AFH in the submandibular region using a full genetic *** SUMMARY A 13-year-old boy who had been misdiagnosed in the past 6 mo by his dentist visited our clinic because of a lesion in the submandibular area on the right *** lesion was homogeneous and painless upon *** skin discoloration was *** to the non-specific radiological picture computed tomography(CT),magnetic resonance imaging(MRI),cone-beam CT(CBCT),and ultrasoundguided biopsy were performed.A venous malformation was suspected on the *** of the tests provided a definitive *** to the non-specific radiological findings,the patient qualified for surgical *** surgical procedure included an excisional *** diagnostic testing was extended using gene *** most distinctive gene translocation in diagnosing AFH is within the EWS RNA-binding protein 1(EWSR1)-CREB-binding ***,in this case,the diagnosis was confirmed by a rearrangement within the EWSR1 gene *** AFH in the submandibular location is rare,and surgical treatment with genetic evaluation defines AFH type that affects subsequent procedures.

关键词： Angiomatoid fibrous histiocytoma Head and neck Fine-needle aspiration CREB-binding protein Gene expression Computed tomography Case report

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Three-Dimensional Modeling of Shallow Shear-Wave Velocities for Las Vegas, Nevada, Using Sediment Type

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Journal of China University of Geosciences 2009年第3期20卷 555-562页

作者： barbara Luke Helena Murvosh Wanda Taylor Jeff Wagoner University of Nevada Las Vegas Las Vegas NV USA Stanley Consultants Inc. Las Vegas NV USA Lawrence Livermore National Laboratory Livermore CA USA

A three-dimensional model of near-surface shear-wave velocity in the deep alluvial basin underlying the metropolitan area of Las Vegas, Nevada （USA）, is being developed for earthquake site response projections. The velocity dataset, which includes 230 measurements, is interpolated across the model using depth-dependent correlations of velocity with sediment type. The sediment-type database contains more than 1 400 well and borehole logs. Sediment sequences reported in logs are assigned to one of four units. A characteristic shear-wave velocity profile is developed for each unit by analyzing closely spaced pairs of velocity profiles and well or borehole logs. The resulting velocity model exhibits reasonable values and patterns, although it does not explicitly honor the measured shear-wave velocity profiles. Site response investigations that applied a preliminary version of the velocity model support a two-zone ground-shaking hazard model for the valley. Areas in which clay predominates in the upper 30 m are predicted to have stronger ground motions than the rest of the basin.

关键词： shear-wave velocity earthquake site response site amplification microzonation sediment type.

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New insights into genetic predisposition and novel therapeutic targets for nonalcoholic fatty liver disease

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Hepatobiliary Surgery and Nutrition 2018年第5期7卷 372-381页

作者： Mary barbara Andrea Scott Naim Alkhouri Department of Medicine University of Texas(UT)Health San AntonioSan AntonioTXUSA Texas Liver Institute San AntonioTXUSA

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the United States affecting 80–100 million Americans. NAFLD encompasses a spectrum of diseases ranging from excess liver fat (nonalcoholic fatty liver or NAFL), to necro-inflammation (nonalcoholic steatohepatitis or NASH), to fibrosis/ cirrhosis, and malignant transformation (hepatocellular carcinoma). Susceptibility to NAFLD is highly variable and it remains unclear why some patients with NAFLD exhibit NASH, whereas patients with known risk factors have NAFL only. The reasons for this variability can be a partially attributed to differences in genetic background. In the last decade, there have been multiple genome wide association studies, which have enriched our understanding of the genetic basis of NAFLD. The I148M PNPLA3 (patatin-like phospholipase domain-containing protein 3) variant has been identified as the major common genetic determinant of NAFLD. Variants with moderate effect size like TM6SF2, MBOAT7 and GCKR have also been shown to have a significant contribution. New research has uncovered major pathways leading to disease development and progression;therefore, multiple medications are being developed and tested for the treatment of advanced NAFLD. These agents target metabolic mechanisms as well as inflammation and fibrosis pathways. Several randomized clinical trials (RCTs) are evaluating the efficacy of these novel agents on histological improvement of disease severity and decreasing liver-related outcomes. FDA-approved medications for NASH and NASH-related fibrosis are expected by 2020.

关键词： Nonalcoholic fatty liver disease (NAFLD) nonalcoholic steatohepatitis (NASH) treatment polymorphism clinical trial

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Precracking and interfacial delamination in a bi-material structure:Static and dynamic loadings

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Acta Mechanica Sinica 2011年第1期27卷 80-89页

作者： barbara Gambin Jordanka Ivanova Varbinka Valeva Gergana Nikolova Institute of Fundamental Technological Research Institute of Mechanics

The behavior of a precracked bi-material structure interface under given static and dynamic axial loading is an interest object in the present ***,it is shown that the shear-lag model is a proper tool to analyze a delamination process in a precracked bi-material structure undergoing static ***,the＂shear-lag model＂is applied to the structure under dynamic *** solve the problem for an interface delamination of the structure and to determine the debond length along the interface,our own 2D boundary element method（BEM）code is proposed in the case of static loading,and the shear-lag model together with the Laplace transforms and half-analytical calculations are used in the case of dynamic *** interface layer is assumed as a very thin plate compared with the other *** parametric（geometric and elastic）analysis of the debond length and interface shear stress is done. The results from the 2D BEM code proved the validity of analytical solutions to the shear-lag *** the dynamic case,the influence of loading characteristics,i.e.,frequencies and amplitude fluctuations on the shear stress and the value of debond length for an interval of time,is discussed. The analysis of the obtained results is illustrated by an example of the modern ceramic-metal composite,namely cermet, and depicted in figures.

关键词： Debond length · Precracked bi-material structure · Shear-lag model · Delamination · BEM

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