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Nitric oxide:A potential key point of the signaling network leading to plant secondary metabolite biosynthesis

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Progress in Natural Science:Materials International 2007年第12期17卷 1397-1404页

作者： Xu Maojun(Department of Biotechnology, Zhejiang Gongshang University, Hangzhou 310035, China) Department of Biotechnology Zhejiang Gongshang University Hangzhou 310035 China

The endogenous signaling network of plants plays important roles in mediating the exogenous factor-induced biosynthesis of secondary metabolites. Nitric oxide (NO) has emerged as a key signaling molecule in plants recently. Numerous studies demonstrated that the main signaling molecules such as salicylic acid (SA), jasmonic acid (JA), reactive oxygen species (ROS), and NO were not only involved in regulating plant secondary metabolite biosynthesis but also interacted to form a complex signaling network by mutual inhibition and/or synergy. The recent progress in the signal network of plant secondary metabolite biosynthesis has been discussed in this paper. Furthermore, we propose a hypothetical model to show that NO might act as a potential molecular switch in the signaling network leading to plant secondary metabolite biosynthesis.

关键词： plant secondary metabolites biosynthesis signaling network nitric oxide salicylic acid jasmonic acid reactive oxygen species.

McSNAC:A software to approximate first-order signaling networks from mass cytometry data

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Quantitative Biology 2023年第1期11卷 59-71页

作者： Darren Wethington Sayak Mukherjee Jayajit Das Steve and Cindy Rasmussen Institute for Genomic Medicine Abigail Wexner Research InstituteNationwide Children’s HospitalColumbusOhio 43205United States Biomedical Sciences Graduate Program College of MedicineThe Ohio State UniversityColumbusOhio 43210United States Department of Pediatrics College of MedicineThe Ohio State UniversityColumbusOhio 43210United States Pelotonia Institute for Immuno-Oncology College of MedicineThe Ohio State UniversityColumbusOhio 43210United States DepartmentofBiomedicalInformatics CollegeofMedicineTheOhioStateUniversityColumbusOhio43210United States Biophysics Graduate Program The Ohio State UniversityColumbusOhio 43210United States Battelle Memorial Institute ColumbusOhio 43201United States

Background:Mass cytometry(CyTOF)gives unprecedented opportunity to simultaneously measure up to 40 proteins in single cells,with a theoretical potential to reach 100 *** high-dimensional single-cell information can be very useful in dissecting mechanisms of cellular *** particular,measuring abundances of signaling proteins like phospho-proteins can provide detailed information on the dynamics of single-cell signaling ***,computational analysis is required to reconstruct such networks with a mechanistic ***:We propose our Mass cytometry signaling network Analysis Code(McSNAC),a new software capable of reconstructing signaling networks and estimating their kinetic parameters from CyTOF *** approximates signaling networks as a network of first-order reactions between *** assumption often breaks down as signaling reactions can involve binding and unbinding,enzymatic reactions,and other nonlinear ***,McSNAC may be limited to approximating indirect interactions between protein species,as cytometry experiments are only able to assay a small fraction of protein species involved in ***:We carry out a series of in silico experiments here to show(1)McSNAC is capable of accurately estimating the ground-truth model in a scalable manner when given data originating from a first-order system;(2)McSNAC is capable of qualitatively predicting outcomes to perturbations of species abundances in simple second-order reaction models and in a complex in silico nonlinear signaling network in which some proteins are ***:These findings demonstrate that McSNAC can be a valuable screening tool for generating models of signaling networks from time-stamped CyTOF data.

关键词： single-cell CyTOF data signaling network kinetics ODE McSNAC

Comparative Analysis of Human Genes Frequently and Occasionally Regulated by m^6A Modification

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Genomics, Proteomics & Bioinformatics 2018年第2期16卷 127-135页

作者： Yuan Zhou Qinghua Cui Department of Biomedical Informatics School of Basic Medical Sciences Peking University

The m^6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m^6A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m^6A modification （m^6Afreq genes） and those occasionally regulated by m^6A modification （m^6Aocca genes）. Compared to the m^6Aocca genes, the m^6Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. signaling network analysis indicates that the m^6Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m^6Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m^6A epitranscriptomic regulation and other gene expression regulatory machineries.

关键词： m^6A Epitranscriptome signaling network Gene expression regulation Gene importance

network-based identification of feedback modules that control RhoA activity and cell migration

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Journal of Molecular Cell Biology 2015年第3期7卷 242-252页

作者： Tae-Hwan Kim Naser Monsefi Je-Hoon Song Alex von Kriegsheim Drieke Vandamme Olivier Pertz Boris NKholodenko Walter Kolch Kwang-Hyun Cho Department of Bio and Brain Engineering Korea Advanced Institute of Science and Technology(KAIST)Daejeon 305-701Republic of Korea Systems Biology Ireland University College DublinBelfieldDublin 4Ireland Department of Biomedicine University of BaselBaselSwitzerland School of Medicine and Medical Science University College DublinBelfieldDublin 4Ireland Conway Institute of Biomolecular&Biomedical Research University College DublinBelfieldDublin 4Ireland

Cancer cell migration enables metastatic spread causing most cancer ***-family GTPases control cell migration,but being embedded in a highly interconnected feedback network,the control of their dynamical behavior during cell migration remains *** address this question,wereconstructed the Rho-family GTPases signaling network involved in cell migration,and developed a Boolean network model to analyze the different states and emergent rewiring of the Rho-family GTPases signaling network at protrusions and during extracellular matrix-dependent cell *** simulations and experimental validations revealed that the bursts of RhoA activity induced at protrusions by EGFare regulated by a negative-feedback module composed of Src,FAK,and ***,perturbing this module interfered with cyclic Rho activation and extracellular matrix-dependent migration,suggesting that CSK inhibition can be a novel and effective intervention strategy for blocking extracellular matrix-dependent cancer cell migration,while Src inhibition might fail,depending on the genetic background of ***,this study provides new insights into the mechanisms that regulate the intricate activation states of Rho-family GTPases during extracellular matrix-dependent migration,revealing potential new targets for interfering with extracellular matrix-dependent cancer cell migration.

关键词： cell migration Rho-family GTPases signaling network Boolean network model cyclical RhoA bursts

Fetal liver： an ideal niche for hematopoietic stem cell expansion

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Science China(Life Sciences) 2018年第8期61卷 885-892页

作者： Suwei Gao Feng Liu College of Life Sciences Hebei UniversityBaoding 071002China State Key Laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China

Fetal liver （FL） is an intricate and highly vascularized hematopoietic organ, which can support the extensive expansion of hematopoietic stem cells （HSCs） without loss of stenmess, as well as of the downstream lineages of HSCs. This powerful function of FL largely benefits from the niche （or microenvironment）, which provides a residence for HSC expansion. Numerous studies have demonstrated that the FL niche consists of heterogeneous cell populations that associate with HSCs spatially and regulate HSCs functionally. At the molecular level, a complex of cell extrinsic and intrinsic signaling network within the FL niche cells maintains HSC expansion. Here, we summarize recent studies on the analysis of the FL HSCs and their niche, and specifically on the molecular regulatory network for HSC expansion. Based on these studies, we hypothesize a strategy to obtain a large number of functional HSCs via 3D reconstruction of FL organoid ex vivo for clinical treatment in the future.

关键词： fetal liver niche hematopoietic stem cell expansion signaling network

System control-mediated drug delivery towards complex systems via nanodiamond carriers

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International Journal of Smart and Nano Materials 2010年第1期1卷 69-81页

作者： Dean Ho Chih-Ming Ho Department of Biomedical Engineering Department of Mechanical Engineering Northwestern UniversityEvanstonIL 60208USA Robert H.Lurie Comprehensive Cancer Center Northwestern UniversityChicagoIL 60611USA Department of Mechanical and Aerospace Engineering University of CaliforniaLos AngelesLACA 90095USA Center for Cell Control A NIH Nanomedicine Development CenterLos AngelesCA 90095USA

Cells represent the basic units of life and contain an intertwined network of signaling and regulatory circuitries that drive the processes of *** processes include the mediation of mechano-sensation,onset of and protection against disease,inflammation,and *** the network of bio-complex systems,each pathway interacts nonlinearly with others through different molecular *** a result,specific functionalities can not be simply linked to the cellular molecules in isolation.A complex system generally possesses very rich information content that can be characterized by the following features:(i)they contain a large number of building blocks;(ii)their interactions among building blocks and with their environment;(iii)they display organization without an external organizing principle being applied;and(iv)they exhibit adaptability and *** properties account for the innate intelligence of biology and its ability to regulate its homeostatic ***,this same complexity underlies,in cancer for example,challenges towards disease management,as the addressing of singular pathways with therapeutic compounds is not ***,combinatorial therapy often serves as a key strategy towards tumor *** iterative searching for optimized therapeutic combinations is indeed a daunting,if not preclusive task,we introduce the feedback system control(FSC)scheme,which may serve as a clinically relevant approach,provided a translational approach towards drug delivery is *** to their innate biocompatibility,which has been comprehensively observed,as well as their ability to delivery virtually any type of therapeutic in a sustained fashion due to their unique surface properties,nanodiamonds may serve as a foundation for nanoenabled combinatorial therapy.

关键词： bio-complex system feedback system control drug delivery,nanodiamond combinatorial medicine signaling network nanomedicine

Differential signaling regulatory networks governing hormone refractory prostate cancers

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Journal of Chinese Pharmaceutical Sciences 2014年第8期23卷 511-524页

作者： Sujit Nair Celine Liew Tin Oo Khor Li Cai Ah-Ng Kong Amrita Cancer Discovery Biology Laboratory and Amrita School of Pharmacy Amrita Vishwa Vidyapeetham UniversityPonekkara P.O. Kochi-682041 Kerala India Department of Pharmaceutics Rutgers The State University of New Jersey Piscataway NJ-08854 USA Department of Pharmacy National University of Singapore Singapore-117543 Republic of Singapore Department of Biomedical Engineering Rutgers The State University of New Jersey Piscataway NJ-08854 USA

To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer （HRPC）, we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rvl and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer （PCa） cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site （TFBS） signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ＇target hubs＇ were identified in the current study including AP-1, NF-KB, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia （HG-PIN） and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ＇target hubs＇ in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.

关键词： Prostate cancer signaling network Target hub Regulatory network Biomarker Transcription Factor Binding Site