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Repression of the Auxin Response Pathway Increases Arabidopsis Susceptibility to Necrotrophic Fungi

Molecular Plant 2008年第3期1卷 496-509页

作者： Francisco Llorente Paul M usksktt Andrea sanchez-Vallet Gemma Lopez Brisa Ramos clara sanchez-rodriguez Lucia Jorda Jane Parker Antonio Molina Centro de Biotecnologia y Genbmica de Plantas (CBGP) Departamento de Biotecnologia-UPM ETS Ingenieros Agrbnomos Avda Complutense E-28040Madrid Spain Department of Plant-Microbe Interactions Max Planck Institute for Plant Breeding Research Carl-von-Linne Weg 10 50829 Cologne Germany

In plants, resistance to necrotrophic pathogens depends on the interplay between different hormone systems, such as those regulated by salicylic acid （SA）, jasmonic acid （JA）, ethylene, and abscisic acid. Repression of auxin signaling by the SA pathway was recently shown to contribute to antibacterial resistance. Here, we demonstrate that Arabidopsis auxin signaling mutants axrl, axr2, and axr6 that have defects in the auxin-stimulated SCF （Skpl-Cullin- F-box） ubiquitination pathway exhibit increased susceptibility to the necrotrophic fungi Plectosphaerella cucumerina and Botrytis cinerea. Also, stabilization of the auxin transcriptional repressor AXR3 that is normally targeted for removal by the SCF-ubiquitin/proteasome machinery occurs upon P. cucumerina infection. Pharmacological inhibition of auxin transport or proteasome function each compromise necrotroph resistance of wild-type plants to a similar extent as in non-treated auxin response mutants. These results suggest that auxin signaling is important for resistance to the necrotro- phic fungi P. cucumerina and B. cinerea. SGTlb （one of two Arabidopsis SGT1 genes encoding HSP90/HSC70 co-chaperones） promotes the functions of SCF E3-ubiquitin ligase complexes in auxin and JA responses and resistance conditioned by certain Resistance （R） genes to biotrophic pathogens. We find that sgtlb mutants are as resistant to P. cucumerina as wild-type plants. Conversely, auxin/SCF signaling mutants are uncompromised in RPP4-triggered resistance to the obligate biotrophic oomycete, Hyaloperonospora parasitica. Thus, the predominant action of SGTlb in R gene-conditioned resis- tance to oomycetes appears to be at a site other than assisting SCF E3-ubiquitin ligases. However, genetic additivity of sgtlb axrl double mutants in susceptibility to H. parasitica suggests that SCF-mediated ubiquitination contributes to lim- iting biotrophic pathogen colonization once plant-pathogen compatibility is established.

关键词： plant defense innate immunity necrotrophic fungi auxin signaling proteasome.

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Arabidopsis Heterotrimeric G-protein Regulates Cell Wall Defense and Resistance to Necrotrophic Fungi

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Molecular Plant 2012年第1期5卷 98-114页

作者： Magdalena Delgado-Cerezo clara sanchez-rodriguez Viviana Escudero Eva Miedes Paula Virginia Fernandez Lucia Jorda Camilo Hernandez-Blanco Andrea sanchez-Vallet Pawel Bednarek Paul Schulze-Lefert Shauna Somervilleg Jose Manuel Estevez Staffan Persson Antonio Molina Centro de Biotecnologia y Genomica de Plantas （UPM-INIA） Universidad Politecnica de Madrid Campus de Montegancedo E-28223-Pozuelo de Alarcbn （Madrid） Spain Max-Planck-lnstitute fLir Molekulare Pflanzenphysiologie Am MQhlenberg 2 14476 Potsdam Germany Laboratorio de Fisiologia y Biologia Molecular IFIByNE （CONICET） FCEyN-Universidad de Buenos Aires Pab. II Intendente Guiraldes 2160 Buenos Aires C1428EGA Argentina Present address： Laboratory of Phytopathology Wageningen University Droevendaalsesteeg 1 6708 PB Wageningen The Netherlands Max Planck Institut for Zuchtungsforschung Department of Plant Microbe Interactions Carl-von-Linne-Weg 10 D-50829 Koln Germany Institute of Bioorganic Chemistry Polish Academy of Sciences Noskowskiego 12/14 61-704 Poznan Poland Energy Biosciences Institute 130 Calvin Hall University of California at Berkeley Berkeley CA 94720 USA

The Arabidopsis heterotrimeric G-protein controls defense responses to necrotrophic and vascular fungi. The agbl mutant impaired in the Gβ subunit displays enhanced susceptibility to these pathogens. Gβ/AGB1 forms an obligate dimer with either one of the Arabidopsis Gγsubunits （γ1/AGG1 and γ2/AGG2）. Accordingly, we now demonstrate that the aggl agg2 double mutant is as susceptible as agbl plants to the necrotrophic fungus Plectosphaerella cucumerina. To elucidate the molecular basis of heterotrimeric G-protein-mediated resistance, we performed a comparative transcriptomic analysis of agbl-1 mutant and wild-type plants upon inoculation with P cucumerina. This analysis, together with metab- olomic studies, demonstrated that G-protein-mediated resistance was independent of defensive pathways required for resistance to necrotrophic fungi, such as the salicylic acid, jasmonic acid, ethylene, abscisic acid, and tryptophan-derived metabolites signaling, as these pathways were not impaired in agbl and aggl agg2 mutants. Notably, many mis-reguiated genes in agbl plants were related with cell wall functions, which was also the case in aggl agg2 mutant. Biochemical analyses and Fourier Transform InfraRed （FTIR） spectroscopy of cell walls from G-protein mutants revealed that the xylose content was lower in agbl and aggl agg2 mutants than in wild-type plants, and that mutant walls had similar FTIR spec-tratypes, which differed from that of wild-type plants. The data presented here suggest a canonical functionality of the Gβ and Gγ1/γ2 subunits in the control of Arabidopsis immune responses and the regulation of cell wall composition.

关键词： Plant immunity cell wall indole glucosinolates xylose necrotropic fungi G-protein.

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The Cellulose Synthases Are Cargo of the TPLATE Adaptor Complex

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Molecular Plant 2018年第2期11卷 346-349页

作者： clara sanchez-rodriguez Yanyun Shi Christopher Kesten Dongmei Zhang Gloria Sancho-Andres Alexander Ivakov Edwin R. Lampugnani Kamil Sklodowski Masaru Fujimoto Akihiko Nakano Antony Bacic Ian S. Wallace Takashi Ueda Daniel Van Damme Yihua Zhou Staffan Persson Max-Planck-lnstitute for Molecular Plant Physiology Am Muehlenberg 1 14476 Potsdam Germany Department of Biology ETH Zurich 8092 Zurich Switzerland State Key Laboratory of Plant Genomics Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China School of Biosciences University of Melbourne Parkvine 3010 VIC Australia ARC Centre of Excellence for Translational Photosynthesis Research School of Biology Australian National University GPO Box 475 Canberra ACT 2601 Australia Department of Biological Sciences Graduate School of Science The University of Tokyo Hongo Bunkyo-ku Tokyo 113-0033 Japan Live Cell Super-resolution Imaging Research Team RIKEN Center for Advances Photonics Hirosawa Wako Saitama 351-0198 Japan ARC Centre of Excellence in Plant Cell Walls School of Biosciences University of Melbourne Parkville 3010 VIC Australia Department of Biochemistry and Molecular Biology University of Nevada Reno NV 89557 USA Division of Cellular Dynamics National Institute for Basic Biology Okazaki Aichi 444-8585 Japan Department of Plant Biotechnology and Bioinformatics Ghent University 9052 Gent Belgium Center for Plant Systems Biology VIB Technologiepark 927 9052 Gent Belgium present address: Laboratory of Plant Molecular Genetics Graduate School of Agricultural and Life Sciences The University of Tokyo 1-1-1 Yayoi Bunkyo-ku Tokyo 113-8657 Japan

Dear Editor Clathrin-mediated endocytosis （CME） is an evolutionary conserved mechanism by which plasma membrane （PM）-based cargo proteins are recognized by adaptor protein complexes and internalized. Apart from the canonical adaptor complex, AP-2, plant cells rely on the TPLATE complex （TPC） to execute CME （Gadeyne et al., 2014）. FT160100218, DP110100410）, the Ministry of Education, Culture, Sports, Science, and Technology of Japan （24114003, 15H04382, and 17K19412）, the European Research Council （ERC grant 682436）, the IRRTF-RNC （no. 501892） and a USA National Science Foundation CAREER Award.

关键词： CLATHRIN-MEDIATED ENDOCYTOSIS ARABIDOPSIS MEMBRANE

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Astrocytes and retrograde degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease:removing axonal debris

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Translational Neurodegeneration 2021年第4期10卷 554-572页

作者： Ingrid Morales Ricardo Puertas-Avendaño Alberto sanchez Adrian Perez-Barreto clara rodriguez-Sabate Manuel rodriguez Laboratory of Neurobiology and Experimental Neurology Department of Basic Medical SciencesFaculty of MedicineLa Laguna UniversityLa LagunaTenerifeCanary IslandsSpain Center for Networked Biomedical Research on Neurodegenerative Diseases(CIBERNED) MadridSpain

Objective:The dopaminergic nigrostriatal neurons(DA cells)in healthy people present a slow degeneration with aging,which produces cellular debris throughout *** 2%-5%of people present rapid cell degeneration of more than 50%of DA cells,which produces Parkinson's disease(PD).Neuroinflammation accelerates the cell degeneration and may be critical for the transition between the slow physiological and the rapid pathological degeneration of DA cells,particularly when it activates microglial cells of the medial forebrain bundle near dopaminergic *** synaptic debris produced by DA cell degeneration may trigger the parkinsonian neuroinflammation,this study investigated the removal of axonal debris produced by retrograde degeneration of DA cells,paying particular attention to the relative roles of astrocytes and ***:Rats and mice were injected in the lateral ventricles with 6-hydroxydopamine,inducing a degeneration of dopaminergic synapses in the striatum which was not accompanied by non-selective tissue damage,microgliosis or *** possible retrograde degeneration of dopaminergic axons,and the production and metabolization of DA-cell debris were studied with immunohistochemical methods and analyzed in confocal and electron microscopy ***:The selective degeneration of dopaminergic synapses in the striatum was followed by a retrograde degeneration of dopaminergic axons whose debris was found within spheroids of the medial forebrain *** spheroids retained mitochondria and most(e.g.,tyrosine hydroxylase,the dopamine transporter protein,and amyloid precursor protein)but not all(e.g.,α-synuclein)proteins of the degenerating dopaminergic *** showed initial(autophagosomes)but not late(lysosomes)components of autophagy(incomplete autophagy).These spheroids were penetrated by astrocytic processes of the medial forebrain bundle,which provided the lysosomes needed to continue the degradation of dopaminergic debri

关键词： Astrocyte Phagocytosis Parkinson's disease Dying-back degeneration Medial forebrain bundle Spheroid

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Optimizing the delivery of combination therapy for tumors： A mathematical model

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International Journal of Biomathematics 2017年第3期10卷 179-194页

作者： clara Rojas rodriguez Juan Belmonte-Beitia Departamento de Matematicas E. T. S. de Ingenieros Industriales Universidad de CastiUa-La Mancha 13071 Ciudad Real Spain Instituto de Matemdtica Aplicada a la Ciencia y la Ingenierla (IMA CI) Universidad de Castilla-La Mancha 13071 Ciudad Real Spain

We present in this paper a new mathematical model for the scheduling of angiogenic inhibitors in combination with a chemotherapeutic agent for a tumor. Our model takes into account the process of angiogenesis and the quality of the vasculature discriminating between stable blood vessels and unstable blood vessels. We characterize theoretically the optimal controls on drug distribution to minimize the number of cancer cells at the end of the treatment in a free horizon time problem with restrictions on the total amount of drug doses. Finally, we solve the optimal control problem by using numerical simulations, obtaining as a result that, despite the number of the tumor cells decrease with anti-angiogenic treatment, the best results are reached at the end of the chemotherapy treatment.

关键词： Mathematical modeling of tumor growth anti-angiogenic treatment chemotherapy singular control bang–bang control

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Wavelet-based deconvolution of ultrasonic signals in nondestructive evaluation

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2006年第10期7卷 1748-1756页

作者： HERRERA Roberto Henry OROZCO Rubén rodriguez Manuel Department of Informatics University of Cienfuegos Cienfuegos 59430 Cuba CEETI Central University of Las Villas Santa Clara 54830 Cuba Department of Physics Central University of Las Villas Santa Clara 54830 Cuba

In this paper, the inverse problem of reconstructing reflectivity function of a medium is examined within a blind deconvolution framework. The ultrasound pulse is estimated using higher-order statistics, and Wiener filter is used to obtain the ultrasonic reflectivity function through wavelet-based models. A new approach to the parameter estimation of the inverse filtering step is proposed in the nondestructive evaluation field, which is based on the theory of Fourier-Wavelet regularized deconvolution (ForWaRD). This new approach can be viewed as a solution to the open problem of adaptation of the ForWaRD framework to perform the convolution kernel estimation and deconvolution interdependently. The results indicate stable solutions of the esti- mated pulse and an improvement in the radio-frequency (RF) signal taking into account its signal-to-noise ratio (SNR) and axial resolution. Simulations and experiments showed that the proposed approach can provide robust and optimal estimates of the reflectivity function.

关键词：盲反褶积超声波信号处理小波规则化

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Precision medicine in sepsis and septic shock:From omics to clinical tools

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World Journal of Critical Care Medicine 2022年第1期11卷 1-21页

作者： Juan Carlos Ruiz-rodriguez Erika P Plata-Menchaca Luis Chiscano-Camón Adolfo Ruiz-Sanmartin Marcos Pérez-Carrasco clara Palmada Vicent Ribas Mónica Martínez-Gallo Manuel Hernández-González Juan J Gonzalez-Lopez Nieves Larrosa Ricard Ferrer Intensive Care Department Vall d’Hebron Hospital UniversitariVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Shock Organ Dysfunction and Resuscitation Research GroupVall d’Hebron Institut de Recerca(VHIR)Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Departament de Medicina Universitat Autònoma de BarcelonaBellaterra 08193Spain Department of Intensive Care Hospital Clínic de BarcelonaBarcelona 08036Spain Data Analytics in Medicine Digital Health UnitEurecatCentre Tecnològic de CatalunyaBarcelona 08005Spain Immunology Division Vall d’Hebron Hospital UniversitariVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Diagnostic Immunology Research Group Vall d’Hebron Institut de Recerca(VHIR)Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Department of Cell Biology Physiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterra 08193Spain Department of Clinical Microbiology Vall d’Hebron Hospital UniversitariVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Department of Microbiology and Genetics Universitat Autònoma de BarcelonaBellaterra 08193Spain

Sepsis is a heterogeneous disease with variable clinical course and several clinical *** it is associated with an increased risk of death,patients with this condition are candidates for receipt of a very well-structured and protocolized *** patients should receive the fundamental pillars of sepsis management,which are infection control,initial resuscitation,and multiorgan ***,specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological ***,we will review the framework for identifying subpopulations of patients with sepsis,septic shock,and multiorgan dysfunction who may benefit from specific *** of these approaches are still in the early stages of research,while others are already in routine use in clinical practice,but together will help in the effective generation and safe implementation of precision medicine in sepsis.

关键词： Sepsis Septic shock Organ dysfunction Precision medicine Biomarkers Phenotype Endotype

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An opportunity for improvement with a medication reconciliation programme

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Open Journal of Internal Medicine 2013年第4期3卷 129-134页

作者： Ana Belén Jiménez-Munoz Ana clara Zoni Esther Duran-Garcia Paz rodriguez Pérez Maria Sanjurjo Saez Rosa Pla-Mestre Preventive Medicine Hospital Universitario Severo OchoaMadridSpain Preventive Medicine and Quality Management Department Hospital General Universitario Gregorio MaranonC/Doctor EsquerdoMadridSpain

Medication reconciliation is priority in safety. Between 54% and 67% of hospitalized patients have at least one unintended discrepancies (UDs) between pharmacological treatment of a hospital inpatient and treatment that they were previously taking at home. Quasi-experimental pre-post study performed. The objective is to assess the impact of an intervention aimed at decreasing UDs between medication prescribed on admission and patient’s regular treatment. Patients who were hospitalised for more than 24 hours and were undergoing treatment prior to admission which involved taking three or more medicines were included. The number of patients included was 331 and 3781 medicines were reconciled. The incidence of UDs decreased significantly from 7.24% to 4.18%. Omission was the most common UD, with a significant decrease from 5.8% to 3.4%. Respect to clinical impact, we observed that error type C (error reached patient without causing harm) predominates, how- ever, experienced a statistically significant decrease from 5.3% to 2.4%.

关键词： Medication Reconciliation Admission Unintended Discrepancies

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Complete Achilles Tenotomy:A New Improved Experimental Surgical Technique in Rats

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Open Journal of Animal Sciences 2018年第1期8卷 1-11页

作者： Kelly Biancardini Gomes Barbato Guilherme de Almeida Joao da Costa Libardo rodriguez clara Raposo Hanna Dias Renata Paiva Liszt Palmeira de Oliveira Jorge Carvalho Clinical and Experimental Pathophysiology Postgraduate Program School of MedicineState University of Rio de JaneiroRio de JaneiroBrazil Department of Surgical Specialties School of MedicineState University of Rio de JaneiroRio de JaneiroBrazil School of Medicine State University of Rio de JaneiroRio de JaneiroBrazil Department of Histology and Embriology Roberto Alcantara Gomes Institute of BiologyState University of Rio de JaneiroRio de JaneiroBrazil

Rupture of the Achilles tendon is one of the most frequent tendon injuries in humans. However, there is no standard surgical technique thus far to reproduce complete rupture of this tendon in rats. Surgical procedures were performed in Wistar rats under light microscopy, with posterior longitudinal incision and preservation of the plantaris tendon. The animals were sacrificed on 2nd and 8th postoperative week and we used hematoxilin and eosin, picrosirius-red and Weigert’s resorcin-fuchsin to observe general tendon healing. The mean operative time was one minute and 24 seconds. Histological studies showed cellular proliferation and fibrillogenesis at two weeks, with decreased amounts of cellularity and elastic fibers at the 8th week, besides changes in structural organization of collagen fibers. The complete Achilles tenotomy in rats, was improved under light microscopy and sparing the plantaris tendon. This surgical technique was simple and quick, showed signs of normal healing process, could be easily reproducible, and triggered translational researches in this area.

关键词： Achilles Tendon Rupture Animal Experimentation Wound Healing Collagen Elastic Tissue

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Benefits of the Combined Use of NSAID and Early Exercise on Tendon Healing in a Murine Model

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Open Journal of Animal Sciences 2018年第4期8卷 357-369页

作者： Kelly Biancardini Gomes Barbato clara Raposo Hanna Dias Renata Paiva Joao da Costa Libardo rodriguez Guilherme de Almeida Oscar Rocha-Barbosa Liszt Palmeira de Oliveira Jorge Carvalho School of Medicine State University of Rio de JaneiroRio de JaneiroBrazil Department of Surgical Specialties School of MedicineState University of Rio de JaneiroRio de JaneiroBrazil Department of Zoology Roberto Alcantara Gomes Institute of BiologyState University of Rio de JaneiroRio de JaneiroBrazil Department of Histology and Embriology Roberto Alcantara Gomes Institute of BiologyState University of Rio de JaneiroRio de JaneiroBrazil

Achilles tendon rupture is one of the most frequent tendon injuries. The aim of this experimental study was to evaluate the effect of a non-steroidal anti-inflammatory drug (NSAID) and of aerobic exercise, in an isolated fashion and combined, on cell proliferation and on the biomechanical aspects of the Achilles tendon during healing process after a complete tenotomy in 156 male Wistar rats. Half of the animals received an intra-muscular injection of tenoxicam for 7 days and exercise was initiated on the 8th day for half the animals of each group. Animals were sacrificed at 1, 2, 4 and 8 weeks after the tenotomy and cell proliferation was evaluated by immunohistochemistry for PCNA, biomechanical evaluation was performed with ultimate load and gait cycle analysis was also carried out. Animals were divided into four treatment groups: A) no NSAID and no exercise (control group);B) NSAID plus exercise;C) no NSAID, with exercise;D) NSAID and no exercise. We used the test of two-way analysis of variance with equal cells number, Kruskal-Wallis test and also, Bonferroni method, in the R Project program 3.5.0. The highest intensity of PCNA immunostaining was found at 2 weeks in all groups except for group A (control) that had the highest intensity at 1 week. Animals submitted to exercise had significantly higher (P = 0.02) ultimate loads when compared to animals that were not submitted to exercise at 8 weeks after injury. The animals that received NSAID presented with a more stable gait cycle than the animals that did not receive NSAID. Aerobic exercise, initiated early after a complete Achilles tendon tenotomy, was beneficial to the biomechanical aspects of the tendon that occur during tendon regeneration and the combined use of NSAID improved the gait’s characteristics which could be protective against re-ruptures.

关键词： Achilles Tendon Rupture Experimental Study Non-Steroidal Anti-Inflammatory Drug Aerobic Exercise PCNA Biomechanics

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