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Strong Suppression of Systemic Acquired Resistance in Arabidopsis by NRR is Dependent on its Ability to Interact with NPRland its Putative Repression Domain

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Molecular Plant 2008年第3期1卷 552-559页

作者： Mawsheng chern Patrick E. canlas Pamela c. ronald Department of Plant Pathology University of California Davis CA 95616 USA

Systemic Acquired Resistance （SAR） in plants confers lasting broad-spectrum resistance to pathogens and requires the phytohormone salicylic acid （SA）. Arabidopsis NPR1/NIM1 is a key regulator of the SAR response. Studies attempting to reveal the function of NPR1 and how it mediates SA signaling have led to isolation of two classes of proteins that interact with NPRI＂ the first class includes rice NRR, Arabidopsis NIMIN1, NIMIN2, and NIMIN3, and tobacco NIMIN2-1ike proteins; the second class belongs to TGA transcription factors. We have previously shown that overexpression of N RR in rice suppresses both basal and Xa21-mediated resistance. In order to test whether NRR affects SA-induced, NPRl-mediated SAR, we have transformed Arabidopsis with the rice NRR gene and tested its effects on the defense response. Expression of NRR in Arabidopsis results in suppression of PR gene induction by SAR inducer and resistance to pathogens. These phenotypes are even more severe than those of the nprl-1 mutant. The ability of NRR to suppress PR gene induction and disease resistance is correlated with its ability to bind to NPR1 because two point mutations in NRR, which reduce NPR1 binding, fail to suppress NPR1. In contrast, wild-type and a mutant NRR, which still binds to NPR1 strongly, retain the ability to suppress the SAR response. Replacing the c-terminal 79 amino acids of NRR with the VP16 activation domain turns the fusion protein into a transcriptional co-activator. These results indicate that NRR binds to NPR1 in vivo in a protein complex to inhibit transcriptional activation of PR genes and that NRR contains a transcription repression domain for active repression.

关键词： NRR NPR1 SA SAR disease resistance.

Deely’s Augustine: Ethics, Semiosis, and the Revelatory

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Language and Semiotic Studies 2021年第3期7卷 68-85页

作者： ronald c.Arnett Duquesne University USA

The analysis outlines John Deely’s commitment to Augustine’s implications for a valueladen semiotic understanding of postmodern ***’s value-laden project centers on semiotic signification and *** work announces the inexorable link between semiotic theory and the search for understanding that *** uplifts the importance of engaging signs via context and relational association,uniting ethics and ***’s orientation shaped his inquiry on biosemiotics,semioethics,and ongoing discussions of *** inquiry centers on Deely’s explication of value-laden signs that illuminate Augustine’s understanding of existence,comprehended as God’s ***,I explore Deely’s value-laden semiotic mission through an examination of Augustine’s God-filled background narrative assumption.

关键词： semiosis semioethics Augustine Deely signum the revelatory

Envita’s Precision cancer care: 35-Fold Improvement in Response Rates

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Journal of cancer Therapy 2024年第4期15卷 99-120页

作者： Sheba Goklany John c. Oertle III ronald Matthias Jr. Daniel Warren David Medina Rory Sears Robert Zieve Kendra Quart christopher Aussems Jon Moma Shannon Miller Zach Poteet conner coffin courtney Middleton Erika Ware Phylicia Zarnosky Julie Nowak Winlove Suasin Daniel conway chad Burk Ruth Tan-Lim Dino Prato Envita Medical centers Scottsdale AZ USA

New clinical approaches are imperative beyond the widely adopted National comprehensive cancer Network (NccN) guidelines, utilized by prominent cancer institutions. cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical centers over a two-year period. compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.

关键词： Envita Medical centers Late-stage cancer Overall Response Rate Quality of Life circulating Tumor cells (cTcs) Mutant Allele Frequency (MAF) Precision care

Human biochemical genetics: an insight into inborn errors of metabolism

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2006年第2期7卷 165-166页

作者： YU chunli ScOTT c. ronald Laboratory of Biochemical Genetics Emory University Decatur GA 30033 USA center on Human Development and Disability University of Washington Seattle WA 98195 USA

Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.

关键词： Inborn errors of metabolism (IEM). Newborn screening (NRS) Disease phenotype and therapy

chemokine signaling involving chemokine (c-c motif) ligand 2 plays a role in descending pain facilitation

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Neuroscience Bulletin 2012年第2期28卷 193-207页

作者： ronald Dubner Department of Neural and Pain Sciences School of Dentistry & Program in Neuroscience University of Maryland

Objective Despite accumulating evidence on a role of immune cells and their associated chemicals in mecha- nisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain. The present study was undertaken to test the hypothesis that the chemokine （c-c motif） ligand 2 （ccL2）（commonly known as monocyte chemoattractant protein-1） signaling in the rostral ventromedial medulla （RVM）, a pivotal structure in brainstem pain modulatory circuitry, is involved in descending pain facilitation in rats. Methods An L5 spinal nerve ligation （SNL） was produced in rats under pentobarbital anesthesia. Western blot and immunohistochemistry were used to detect the expression levels of ccL2 and ccL2 receptor （ccR2）, and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein （GFAP, astroglial） and cD 11 b （microglial）, respectively. Results SNL induced an increase in ccL2 expression in the RVM, and this returned to the control level at 4 weeks after injury. The induced ccL2 colocalized with NeuN, but not with GFAP and cD1 lb. ccR2 was also upregu- lated by SNL in the RVM, and this increase lasted for at least 4 weeks. ccR2 was colocalized with cD1 lb but not GFAP. Few RVM neurons also exhibited ccR2 staining. Neutralizing ccL2 with an anti-ccL2 antibody （0.2-20 ng） or injecting RS-102895 （0.1-10 pmol）, a ccR2b chemokine receptor antagonist, into the RVM on day 1 after SNL, significantly at- tenuated the established thermal and mechanical hypersensitivity. In addition, injection of recombinant rat ccL2 （0.03-3 pmol） into the RVM induced dose-dependent hyperalgesia, which was prevented by pretreatment with RS-102895 （10 pmol）. Interleukin-β （IL-1]3）, a potent inducer of neuronal ccL2, was also selectively upregulated in RVM reactive as- trocytes. Injection of IL-1 ]3 （120 fmol） into the RVM induced behavioral hyperalgesia, which was blocked by RS-102895 （10 pmol

关键词： monocyte chemoattractant protein-l chemokine (c-c motif) receptor 2 rostral ventromedial medulla neu-ron-glial interaction neuropathic pain rat

construction of a Rice Glycosyltransferase Phylogenomic Database and Identification of Rice-Diverged Glycosyltransferases

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Molecular Plant 2008年第5期1卷 858-877页

作者： Pei-Jian cao Laura E. Bartley Ki-Hong Jung Pamela c. ronald Department of Plant Pathology University of California Davis CA 95616 and the Joint BioEnergy Institute Emeryville CA 94710 USA Institute of Bioinformatics Zhejiang University Hangzhou Zhejiang 310029 China

Glycosyltransferases （GTs; Ec 2.4.x.y） constitute a large group of enzymes that form glycosidic bonds through transfer of sugars from activated donor molecules to acceptor molecules. GTs are critical to the biosynthesis of plant cell walls, among other diverse functions. Based on the carbohydrate-Active enZymes （cAZy） database and sequence ***, we have identified 609 potential GT genes （loci） corresponding to 769 transcripts （gene models） in rice （Oryza sativa）, the reference monocotyledonous species. Using domain composition and sequence similarity, these rice GTs were classified into 40 cAZy families plus an additional unknown class. We found that two Pfam domains of unknown function, PF04577 and PF04646, are associated with GT families GT61 and GT31, respectively. To facilitate functional analysis of this important and large gene family, we created a phylogenomic Rice GT Database （http：//ricephylogenomics. ***/cellwalls/gtJ）. Through the database, several classes of functional genomic data, including mutant lines and gene expression data, can be displayed for each rice GT in the context of a phylogenetic tree, allowing for comparative analysis both within and between GT families. comprehensive digital expression analysis of public gene expression data revealed that most （-80%） rice GTs are expressed. Based on analysis with Inparanoid, we identified 282 ‘rice-diverged＇ GTs that lack orthologs in sequenced dicots （Arabidopsis thaliana, Populus tricocarpa, Medicago truncatula, and Ricinus communis）. combining these analyses, we identified 33 rice-diverged GT genes （45 gene models） that are highly expressed in above-ground, vegetative tissues. From the literature and this analysis, 21 of these loci are excellent targets for functional examination toward understanding and manipulating grass cell wall qualities. Study of the remainder may reveal aspects of hormone and protein metabolism that are critical for rice biology. This list of 33 genes a

关键词： glycosyltransferases GT phylogenetic tree orthologs expression pattern mutant lines phylogenomic database rice cell wall.

Recent Advances in Dissecting Stress-Regulatory crosstalk in Rice

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Molecular Plant 2013年第2期6卷 250-260页

作者： Rita Sharma David De Vleesschauwer Manoj K. Sharma Pamela c. ronald Department of Plant Pathology and Genome center University of California Davis CA 95616 USA Joint BioEnergy Institute Emeryville CA 94710 USA Laboratory of Phytopathology Faculty of Bioscience Engineering Ghent University B-9000 Ghent Belgium Department of Plant Molecular Systems Biotechnology and crop Biotech Institute Kyung Hee University Yongin 446-701 Korea

Biotic and abiotic stresses impose a serious limitation on crop productivity worldwide. Prior or simultaneous exposure to one type of stress often affects the plant response to other stresses, indicating extensive overlap and cross-talk between stress-response signaling pathways. Systems biology approaches that integrate large genomic and prot-eomic data sets have facilitated identification of candidate genes that govern this stress-regulatory crosstalk. Recently, we constructed a yeast two-hybrid map around three rice proteins that control the response to biotic and abiotic stresses, namely the immune receptor XA21, which confers resistance to the Gram-negative bacterium, Xanthomonas oryzae pv. oryzae; NH1, the rice ortholog of NPR1, a key regulator of systemic acquired resistance; and the ethylene-responsive transcription factor, SUBIA, which confers tolerance to submergence stress. These studies coupled with transcriptional profiling and co-expression analyses identified a suite of proteins that are positioned at the interface of biotic and abiotic stress responses, including mitogen-activated protein kinase 5 （OsMPK5）, wall-associated kinase 25 （WAK25）, sucrose non-fermenting-l-related protein kinase-1 （SnRK1）, SUBIA binding protein 23 （SAB23）, and several WRKY family tran- scription factors. Emerging evidence suggests that these genes orchestrate crosstalk between biotic and abiotic stresses through a variety of mechanisms, including regulation of cellular energy homeostasis and modification of synergistic and/or antagonistic interactions between the stress hormones salicylic acid, ethylene, jasmonic acid, and abscisic acid.

关键词： abiotic biotic crosstalk defense response hormone systems biology stress.

Dendroclimatic analysis of white pine (Pinus strobus L.)using long-term provenance test sites across eastern North America

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Forest Ecosystems 2018年第3期5卷 221-235页

作者： Sophan chhin ronald S.Zalesny Jr William c.Parker John Brissette Division of Forestry and Natural Resources West Virginia University322 Percival HallPO Box 6125MorgantownWV26506USA USDA Forest Service Northern Research Station5985Highway KRhinelanderWI 54501USA Ontario Forest Research Institute 1235Queen St.ESault Ste.MarieON P6A 2E5Canada USDA Forest Service Northern Research Station271Mast RoadDurhamNH 03824USA

Background: The main objective of this study was to examine the climatic sensitivity of the radial growth response of 13 eastern white pine(Pinus strobus L.) provenances planted at seven test sites throughout the northern part of the species’ native distribution in eastern North ***: The test sites(i.e., Wabeno, Wisconsin, USA; Manistique, Michigan, USA; Pine River, Michigan, USA; Newaygo,Michigan, USA; Turkey Point, Ontario, canada; Ganaraska, Ontario, canada; and Orono, Maine, USA) examined in this study were part of a range-wide white pine provenance trial established in the early 1960 s in the eastern United States and canada. Principal components analysis(PcA) was used to examine the main modes of variation [first(Pc1) and second(Pc2) principal component axes] in the standardized radial growth indices of the provenances at each test *** year scores for Pc1 and Pc2 were examined in relation to an array of test site climate variables using multiple regression analysis to examine the commonality of growth response across all provenances to the climate of each test site. Provenance loadings on Pc1 and Pc2 were correlated with geographic parameters(i.e., latitude, longitude,elevation) and a suite of biophysical parameters associated with provenance origin ***: The amount of variation in radial growth explained by Pc1 and Pc2 ranged from 43.4% to 89.6%. Dendroclimatic models revealed that white pine radial growth responses to climate were complex and differed among sites. The key dendroclimatic relationships observed included sensitivity to high temperature in winter and summer, cold temperature in the spring and fal(i.e., beginning and end of the growing season), summer moisture stress, potential sensitivity to storminduced damage in spring and fal, and both positive and negative effects of higher winter snowfal. Separation of the loadings of provenances on principal component axes was mainly associated with temperature-related bioclima

关键词： Adaptation climate change Dendrochronology Seed source

Building Expertise on FAIR Through Evolving Bring Your Own Data(BYOD) Workshops: Describing the Data, Software, and Management-focused Approaches and Their Evolution

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Data Intelligence 2024年第2期6卷 429-456页

作者： césar H.Bernabé Lieze Thielemans Rajaram Kaliyaperumal claudio carta Shuxin Zhang celia W.G.van Gelder Nirupama Benis Luiz Olavo Bonino da Silva Santos ronald cornet Bruna dos Santos Vieira Nawel Lalout Ines Henriques Alberto camara Ballesteros Kees Burger Martijn G.Kersloot Friederike Ehrhart Esther van Enckevort chris T.Evelo Alasdair J.G.Gray Marc Hanauer Kristina Hettne Joep de Ligt Arnaldo Pereira Nuria Queralt-Rosinach Erik Schultes Domenica Taruscio Andra Waagmeester Mark D.Wilkinson Egon L.Willighagen Mascha Jansen Barend Mons Marco Roos Annika Jacobsen Biosemantics Group Department of Human GeneticsLeiden University Medical CentreLeidenThe Netherlands NIHR Academic Fellow in General Practice University College London and The Royal Free NHS Foundation Trust National centre for Rare Diseases Istituto Superiore di SanitaRomeItaly Department of Medical Informatics Amsterdam UMC location University of AmsterdamMeibergdreef 9AmsterdamThe Netherlands Amsterdam Public Health Methodology&Digital HealthAmsterdamThe Netherlands Health-Rl UtrechtThe Netherlands Semantics Services and Cybersecurity groupUniversity of TwenteEnschedeThe Netherlands Department of Medical Imaging Radboud Institute for Health SciencesRadboud University Medical CenterNijmegenThe Netherlands Department of Medical BioSciences Radboud University Medical CenterNijmegenThe Netherlands The Duchenne Parent Project VeneendaalThe Netherlands Departamento de Biotecnologia-Biologia Vegetal Escuela Tecnica Superior de Ingenieria AgronomicaAlimentaria y de BiosistemasCentro de Biotecnologia y Genomica de PlantasUniversidad Politecnica de Madrid(UPM)-Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria-CSIC(INIA-CSIC).Campus MontegancedoPozuelo de Alarcon(Madrid)Spain castor AmsterdamThe Netherlands Department of Bioinformatics-BiGcaT Maastricht UniversityMaastrichtThe Netherlands University Medical center Groningen University of GroningenGroningenThe Netherlands Maastricht centre for Systems Biology(MacSBio) Maastricht UniversityMaastrichtThe Netherlands Department of computer Science Heriot-Watt UniversityEdinburghUK INSERM US14-OrphanetPlateforme Maladies RaresParisFrance centre for Digital Scholarship Leiden University LibrariesThe Netherlands center for Molecular Medicine Cancer Genomics NetherlandsDepartment of GeneticsUniversity Medical Center UtrechtUniversity UtrechtThe Netherlands University of Aveiro DETI/IEETAAveiroPortugal GO FAIR Foundation LeidenThe Netherlands The Leiden Academic center for Drug Research LeidenThe Netherlands Micel

Since 2014,"Bring Your Own Data"workshops(BYODs)have been organised to inform people about the process and benefits of making resources Findable,Accessible,Interoperable,and Reusable(FAIR,and the FAIRification process).The BYOD workshops'content and format differ depending on their goal,context,and the background and needs of ***-focused BYODs educate domain experts on how to make their data FAIR to find new answers to research ***-focused BYODs promote the benefits of making data FAIR and instruct project managers and policy-makers on the characteristics of FAIRification ***-focused BYODs gather software developers and experts on FAIR to implement or improve software resources that are used to support ***,these BYODs intend to foster collaboration between different types of stakeholders involved in data management,curation,and reuse(*** experts,trainers,developers,data owners,data analysts,FAIR experts).The BYODs also serve as an opportunity to learn what kind of support for FAIRification is needed from different communities and to develop teaching materials based on practical examples and *** this paper,we detail the three different structures of the BYODs and describe examples of early BYODs related to plant breeding data,and rare disease registries and biobanks,which have shaped the structure of the *** discuss the latest insights into making BYODs more productive by leveraging our almost ten years of training experience in these workshops,including successes and encountered ***,we examine how the participants'feedback has motivated the research on FAIR,including the development of workflows and software.

关键词： FAIR FAIRification FAIR expertise Bring Your Own Data Workshop BYOD