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Molecular classifications of gastric cancers: Novel insights and possible future applications

World Journal of Gastrointestinal Oncology 2017年第5期9卷 194-208页

作者： Silvio Ken Garattini Debora Basile Monica Cattaneo Valentina Fanotto Elena Ongaro Marta Bonotto Francesca V Negri Rosa Berenato Paola Ermacora Giovanni Gerardo Cardellino mariella giovannoni Nicoletta Pella Mario Scartozzi Lorenzo Antonuzzo Nicola Silvestris Gianpiero Fasola Giuseppe Aprile Department of Oncology University and General Hospital Medical Oncology University Hospital Medical Oncology National Cancer InstituteIRCCS Department of Oncology University Hospital

Despite some notable advances in the systemic management of gastric cancer(GC), the prognosis of patients with advanced disease remains overall poor and their chance of cure is anecdotic. In a molecularly selected population, a median overall survival of 13.8 mo has been reached with the use of human epidermal growth factor 2(HER2) inhibitors in combination with chemotherapy, which has soon after become the standard of care for patients with HER2-overexpressing GC. Moreover, oncologists have recognized the clinical utility of conceiving cancers as a collection of different molecularlydriven entities rather than a single disease. Several molecular drivers have been identified as having crucial roles in other tumors and new molecular classifications have been recently proposed for gastric cancer as well. Not only these classifications allow the identification of different tumor subtypes with unique features, but also they serve as springboard for the development of different therapeutic strategies. Hopefully, the application of standard systemic chemotherapy, specifictargeted agents, immunotherapy or even surgery in specific cancer subgroups will help maximizing treatment outcomes and will avoid treating patients with minimal chance to respond, therefore diluting the average benefit. In this review, we aim at elucidating the aspects of GC molecular subtypes, and the possible future applications of such molecular analyses.

关键词：分子的生物学免疫疗法胃的癌症分类指向的治疗

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Tomato fruit as a model for tissue-specific gene silencing in crop plants

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Horticulture Research 2020年第1期7卷 839-845页

作者： Ari Feder Sarah Jensen Anquan Wang Lance Courtney Lesley Middleton Joyce Van Eck Yongsheng Liu James J.giovannoni Boyce Thompson Institute for Plant Research Cornell UniversityIthacaNYUSA Section of Plant Breeding and Genetics Cornell UniversityIthacaNYUSA School of Biotechnology and Food Engineering Hefei University of Technology230009 HefeiChina Section of Plant Biology Cornell UniversityIthacaNYUSA US Department of Agriculture–Agricultural Research Service Robert W.Holley Center for Agriculture and HealthIthacaNYUSA

Use of CRISPR-Cas9(Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-CRISPR-associated 9)-mediated genome editing has proliferated for use in numerous plant species to modify gene function and expression,usually in the context of either transient or stably inherited genetic alternations.While extremely useful in many applications,modification of some loci yields outcomes detrimental to further experimental evaluation or viability of the target organism.Expression of Cas9 under a promoter conferring gene knockouts in a tissue-specific subset of genomes has been demonstrated in insect and animal models,and recently in Arabidopsis.We developed an in planta GFP(green fluorescent protein)assay system to demonstrate fruit-specific gene editing in tomato using a phosphoenolpyruvate carboxylase 2 gene promoter.We then targeted a SET-domain containing polycomb protein,SlEZ2,previously shown to yield pleiotropic phenotypes when targeted via ^(35)S-driven RNA interference and we were able to characterize fruit phenotypes absent additional developmental perturbations.Tissue-specific gene editing will have applications in assessing function of essential genes otherwise difficult to study via germline modifications and will provide routes to edited genomes in tissues that could not otherwise be recovered when their germline modification perturbs their normal development.

关键词： otherwise specific editing

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Developmental and Feedforward Control of the Expression of Folate Biosynthesis Genes in Tomato Fruit

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Molecular Plant 2010年第1期3卷 66-77页

作者： Jeffrey C. Wallera Tariq A. Akhtar Aurora Lara-Nunez Jesse F. Gregory lli Ryan R McQuinn James J. giovannoni Andrew D. Hanson Horticultural Sciences Department University of Florida Gainesville FL 32611 USA Food Science and Human Nutrition Department University of Florida Gainesville FL 32611 USA United States Department of Agriculture-Agricultural Research Service and Boyce Thompson Institute for Plant Research Ithaca NY 14853 USA

Little is known about how plants regulate their folate content, including whether the expression of folate biosynthesis genes is orchestrated during development or modulated by folate levels. Nor is much known about how folate levels impact the expression of other genes. These points were addressed using wild-type tomato fruit and fruit engineered for high folate content. In wild-type fruit, the expression of genes specifying early steps in folate biosynthesis declined during development but that of other genes did not. In engineered fruit overexpressing foreign GTP cyclohy- drolase I and aminodeoxychorismate synthase genes, the expression of the respective endogenous genes did not change, but that of three downstream pathway genes--aminodeoxychorismate lyase, dihydroneopterin aldolase, and mitochondrial folylpolyglutamate synthase--respectively increased by up to 7.8-, 2.8-, and 1.7-fold, apparently in response to the build-up of specific folate pathway metabolites. These results indicate that, in fruit, certain folate pathway genes are developmentally regulated and that certain others are subject to feedforward control by pathway intermediates. Micro- array analysis showed that only 14 other transcripts （of 11 000 surveyed） increased in abundance by two-fold or more in high-folate fruit, demonstrating that the induction of folate pathway genes is relatively specific.

关键词： Folate biosynthesis fruit development metabolic engineering transcript profiling.

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公共的私人空间意大利giovannoni公寓及工作室

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室内设计与装修 2007年第2期 48-53页

作者： Stefano giovannoni Samuele Martelli

意大利著名设计师Stefano giovannoni不久前将一个旧工厂的厂房改建成居家与办公相结合的空间。项目的地点在米兰ViaTortona区附近。改建完成之后，由于其在建筑与室内设计上的特殊性，这个房子几乎成了展览及各类活动的举办地，尤其是s... 详细信息

意大利著名设计师Stefano giovannoni不久前将一个旧工厂的厂房改建成居家与办公相结合的空间。项目的地点在米兰ViaTortona区附近。改建完成之后，由于其在建筑与室内设计上的特殊性，这个房子几乎成了展览及各类活动的举办地，尤其是salone国际设计周期间，这里更是热闹非凡。

关键词：私人空间意大利工作室公寓厂房改建室内设计设计周期设计师

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Understanding development and ripening of fruit crops in an‘omics’ era

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Horticulture Research 2014年第1期1卷 157-166页

作者： Nigel E Gapper James J giovannoni Christopher B Watkins Department of Horticulture Cornell UniversityIthacaNY 14853USA Boyce Thompson Institute for Plant Research Cornell UniversityIthacaNY 14853USA Plant Soiland Nutrition LaboratoryUS Department of Agriculture/Agriculture Research ServiceIthacaNY 14853USA

Next generation sequencing has revolutionized plant biology.Not only has our understanding of plant metabolism advanced using model systems and modern chromatography,but application of‘omics’-based technology has been widely extended to non-model systems as costs have plummeted and efficiency increased.As a result,important fundamental questions relating to important horticultural crops are being answered,and novel approaches with application to industry are in progress.Here we review recent research advances on development and ripening of fruit crops,how next generation sequencing approaches are driving this advance and the emerging future landscape.

关键词： crops driving metabolism

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iTAK： A Program for Genome-wide Prediction and Classification of Plant Transcription Factors, Transcriptional Regulators, and Protein Kinases

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Molecular Plant 2016年第12期9卷 1667-1670页

作者： Yi Zheng Chen Jiao Honghe Sun Hernan G. Rosli Marina A. Pombo Peifen Zhang Michael Banf Xinbin Dai Gregory B. Martin James J. giovannoni Patrick X. Zhao Seung Y. Rhee Zhangjun Fei Boyce Thompson Institute Ithaca NY 14853 USA Instituto de Fisiología Vegetal (INFIVE CONICET-UNLP) La Plata 1900 Argentina Department of Plant Biology Carnegie Institution for Science Stanford CA 94305 USA Samuel Roberts Noble Foundation Ardmore OK 73401 USA Section of Plant Pathology and Plant-Microbe Biology School of Integrative Plant Science Cornell University Ithaca NY 14853 USA USDA-ARS Robert W. Holley Center for Agriculture and Health Ithaca NY 14853 USA

Dear Editor,Transcription factors （TFs） are proteins that regulate the expression of target genes by binding to specific cis-elements in pro-moter regions. Transcriptional regulators （TRs） a）so regulate the expression of target genes; however, they operate indirectly via interaction with the basal transcription apparatus （e.g., TFs）, or by altering the accessibility of DNA to TFs via chromatin remodeling. Another type of regulatory proteins, protein kinases （PKs）,

关键词： Mystery Mendel's Magnesium

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The tomato HIGH PIGMENT1/DAMAGED DNA BINDING PROTEIN 1 gene contributes to regulation of fruit ripening

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Horticulture Research 2019年第1期6卷 1438-1447页

作者： Anquan Wang Danyang Chen Qiyue Ma Jocelyn K.C.Rose Zhangjun Fei Yongsheng Liu James J.giovannoni School of Biotechnology and Food Engineering Hefei University of TechnologyHefei 230009China Boyce Thompson Institute Cornell UniversityIthacaNY 14853USA Plant Biology Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853USA United States Department of Agriculture Robert W.Holley CenterCornell UniversityIthacaNY 14853USA

Fleshy fruit ripening is governed by multiple external and internal cues and accompanied by changes in color,texture,volatiles,and nutritional quality traits.While extended shelf-life and increased phytonutrients are desired,delaying ripening via genetic or postharvest means can be accompanied by reduced nutritional value.Here we report that the high pigment 1(hp1)mutation at the UV-DAMAGED DNA BINDING PROTEIN 1(DDB1)locus,previously shown to influence carotenoid and additional phytonutrient accumulation via altered light signal transduction,also results in delayed ripening and firmer texture,resulting at least in part from decreased ethylene evolution.Transcriptome analysis revealed multiple ethylene biosynthesis and signaling-associated genes downregulated in hp1.Furthermore,the hp1 mutation impedes softening of the pericarp,placenta,columella as well as the whole fruit,in addition to reduced expression of the FRUITFUL2(FUL2)MADS-box transcription factor and xyloglucan endotransglucosylase/hydrolase 5(XTH5).These results indicate that DDB1 influences a broader range of fruit development and ripening processes than previously thought and present an additional genetic target for increasing fruit quality and shelf-life.

关键词： shelf desired governed

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斯蒂芬诺吉奥瓦诺尼

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设计 2012年第1期25卷 120-127,120页

作者：小南 Studio giovannoni（图） Studio giovannoni

斯蒂芬诺·吉奥瓦诺尼认为自己的价值并不是在于给了世界一张多么杰出的椅子或者一个多么惊艳的水果盘，而是给顾窖们一个在杰出的椅子上值得再三咀嚼的人生。

关键词：工业设计工业设计师斯蒂芬诺·吉奥瓦诺尼艺术

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Analysts of spatio-temporal regulation of tomato fruit ripening

Analysts of spatio-temporal regulation of tomato fruit ripen...

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第三届全国植物开花·衰老与采后生物学大会

作者： James giovannoni Plant Molecular Biologist USDA-ARS Robert W.Holley Center

Tomato is a model for genetic, physiological, chemical and nutritional analyses of fruit development, maturation and ripening. Plant hormones including ethylene, ABA and auxin, in addition to a myriad of transcription factors and changes in the epigenome all contribute to ripening control in a complex manner with clear evidence of multiple feedback loops. Natural mutations, transgenic repression/over-expression and gene editing mutants have all given insights into the functions and roles of ripening regulators with new players continually being added to the symphony of participants in fruit development and ripening. We have deployed tissue-specific gene expression profiling to explore the ripening regulome. Resulting gene expression data is freely available through the Tomato Expression Atlas（TEA） at ***. We have used this data to develop and support our hypothesis that key ripening events initiate under the direction of common regulators first in the fruit locule and placental tissues and spread to other fruit tissues including the carpels. A number of new ripening-associated transcription factors consistent with this profile have been identified. Some influence ripening at the level of specific ripening processes such as softening while others exert broader control.

关键词： Tomato fruit ripening spatio-temporal

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A combination therapy of massage and stretching increases parasympathetic nervous activity and improves joint mobility in patients affected by fibromyalgia

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Health 2010年第8期2卷 919-926页

作者： Laura Bazzichi Marco Dini Alessandra Rossi Silvia Corbianco Elisa giovannoni Arianna Consensi Camillo Giacomelli Francesca De Feo Francesca Sernissi Bruno Rossi Stefano Bombardieri 不详

Objective: to investigate how therapeutic mas-sage, combined with stretching, can really con-tribute to the treatment of fibromyalgia (FM) symptoms. Design: Feasibility study. Setting: A single center. Participants: Twenty women having a preexisting diagnosis of FM based on American College of Rheumatology criteria were recruited. Intervention: Subjects received a total of 18 sessions of light massage administered by a physical therapist twice a week and then performed passive stretching exercises. Main out-come measures: heart rate (HR) and Heart Rate variability (HRV), the assessment of joint flexi-bility through elettrogoniometer, the Fibromyal-gia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), and the Borg scale or Rating of Perceived exertion (RPE). Evalua-tions were conducted at the screening visit (T0), immediately at the end of the session of mas-sage (T1) and after completion of 18 sessions (T2). Results: HRV showed an improvement in terms of decreased sympathetic tone and in-crease of parasympathetic tone at the end of treatment. Also joint flexibility showed a sig-nificant improvement at T2 compared with the screening. FIQ, PSQI, RPE did not change. Conclusions: the findings highlight the excellent compliance of FM patients to the combined therapy of massage and stretching, showing an amelioration of muscle stiffness and an improvement of autonomic nervous system with a decrease of sympathetic tone and an increase of parasympathetic tone. The questionnaires did not show any ameliorations, probably because in these patients the perception of quality of life is distorted compared with more objective pa-rameters, such as muscle rigidity, the articular mobility and the autonomic nervous system.

关键词： Fibromyalgia Massage Therapy Stretching Heart Rate Variability Stiffness

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