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

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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.

Properdin deficiency associated with systemic meningococcal disease due to a novel ***337Arg pathogenic variant

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Genes & Diseases 2024年第6期11卷 43-46页

作者： laura Gonzalez-sanchez Ana mei Agudo Anne Van Den Rym maria Isabel Begiristain Alazne Saizar Rebeca Perez de Diego Pilar Nozal Alberto lopez-Lera margarita lopez-Trascasa Fernando Corvillo Complement Research Group Hospital La Paz Institute for Health Research(ldiPAZ)La Paz University HospitalMadrid 28046Spain Center for Biomedical Network Research on Rare Diseases MadridSpain Laboratory of Immunogenetics of Human Diseases IdiPAz Institute for Health ResearchLa Paz University HospitalMadrid 28046Spain Ormaiztegui Clinic Guipuzcoa 20216Spain Immunology Unit La Paz University HospitalMadrid 28046Spain Departamento de medicina Universidad Autonoma de MadridMadrid28029Spain

Properdin(FP)is a soluble glycoprotein with a key role in the regulation of the alternative pathway(AP)of the complement system.1 Neutrophils are the main source of FP,although monocytes,bone marrow progenitors,and T cells also synthesize this complement *** is codified by the gene CFP,located at Xp11.23-p11.3,and formed by 10 exons,of which exons 2 to 10 are translated conforming six thrombospondin type 1 repeats(TSR1-6).

关键词： Xp11.2 glycoprotein progenitor

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

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Science China materials 2020年第1期63卷 147-156页

作者： Eric Volta-Duran Olivia Cano-Garrido Naroa Serna Hector lopez-Laguna laura sanchez-Garcia mireia Pesarrodona Alejandro sanchez-Chardi Ramon mangues Antonio Villaverde Esther Vazquez Ugutz Unzueta Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de microbiologia Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Nanoligent SL Edifici EUREKAUniversitat Autonoma de BarcelonaBellaterra08193 BarcelonaSpain Institut dInvestigacions Biomèdiques Sant Pau and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau08041 BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciencies AmbientalsFacultat de BiologiaUniversitat de BarcelonaAv.Diagonal 64308028 BarcelonaSpain Institute for Research in Biomedicine(IRB Barcelona) The Barcelona Institute of Science and Technology08028 BarcelonaSpain

modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 *** these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

关键词： nanoparticles protein materials recombinant proteins drug delivery self-assembling cancer cell targeting

Role of cytokines in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第27期14卷 4280-4288页

作者： Fausto sanchez-muoz Aaron Dominguez-lopez Jesus K Yamamoto-Furusho Inflammatory Bowel Disease Clinic Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Vasco de Quiroga 15 colonia Sección XVI

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.

关键词： Cytokines Inflammatory bowel disease Crohn's disease Ulcerative colitis Inflammation

A micromirror array with annular partitioning for high-speed random-access axial focusing

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Light(Science & Applications) 2020年第1期9卷 241-255页

作者： Nathan Tessema Ersumo Cem Yalcin Nick Antipa Nicolas Pegard laura Waller Daniel lopez Rikky muller The University of California Berkeley and University of CaliforniaSan Francisco Graduate Program in BioengineeringBerkeleyCA 94720USA Department of Electrical Engineering&Computer Sciences University of CaliforniaBerkeleyCA 94720USA Department of Applied Physical Sciences University of North Carolina at Chapel HillChapel HillNC 27514USA Chan Zuckerberg Biohub San FranciscoCA 94158USA Physical measurement Laboratory National Institute of Standards and TechnologyGaithersburgMD 20899USA

Dynamic axial focusing functionality has recently experienced widespread incorporation in microscopy,augmented/virtual reality(AR/VR),adaptive optics and material ***,the limitations of existing varifocal tools continue to beset the performance capabilities and operating overhead of the optical systems that mobilize such *** varifocal tools that are the least burdensome to operate(*** crystal,elastomeric or optofluidic lenses)suffer from low(≈100 Hz)refresh ***,the fastest devices sacrifice either critical capabilities such as their dwelling capacity(*** gradient lenses or monolithic micromechanical mirrors)or low operating overhead(*** mirrors).Here,we present a general-purpose random-access axial focusing device that bridges these previously conflicting features of high speed,dwelling capacity and lightweight drive by employing lowrigidity micromirrors that exploit the robustness of defocusing phase ***,the device consists of an 8.2mm diameter array of piston-motion and 48-μm-pitch micromirror pixels that provide 2πphase shifting for wavelengths shorter than 1100 nm with 10-90% settling in 64.8μs(i.e.,15.44 kHz refresh rate).The pixels are electrically partitioned into 32 rings for a driving scheme that enables phase-wrapped operation with circular symmetry and requiresments demonstrated the array’s wide focusing range with a measured ability to target 29 distinct resolvable depth ***,the features of the proposed array offer the potential for compact,straightforward methods of tackling bottlenecked applications,including high-throughput single-cell targeting in neurobiology and the delivery of dense 3D visual information in AR/VR.

关键词： mirror axial random

First report of L1014F kdr mutation in Culex quinquefasciatus in mexico

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Insect Science 2016年第6期23卷 829-834页

作者： Gustavo Ponce Iram P. sanchez Selene m. Garcia Jose m. Torrado Saul Lozano-Fuentes Beatriz lopez-monroy Adriana E. Flores Facultad de Ciencias Biologicas Universidad Autonoma de Nuevo Leon A v. Universidad sin Cd. Universitaria San Nicolas de los GarzaN.L. 66455 Mexico Department of microbiology Immunology and Pathology Colorado State University Fort Collins CO USA

The L1014F mutation in the voltage-sodium channel gene has been associated with resistance to DDT and pyrethroids in various arthropod species including mosquitoes. We determined the frequency of the L1014F kdr mutation in 16 field populations of Culex quinquefasciatus from Northeastern mexico collected between 2008 and 2013. The L1014F was present in all populations analyzed with the lowest frequency （3.33%） corresponding to the population from monclova collected in 2012, and the highest frequency （63.63%） from the monterrey population collected in 2012. The presence of a kdr mutation in populations of Cx. quinquefasciatus from northeastern mexico provides evidence ofpyrethroid resistance. This requires a special attention, considering that pyrethroid-based insecticides are commonly used in vector-control campaigns, especially against Aedes aegypti （L.）.

关键词： Culex quinquefasciatus insecticide resistance kdr L 1014F mutation

Redox Regulation of Glycogen Biosynthesis in the Cyanobacterium Synechocystis sp. PCC 6803： Analysis of the AGP and Glycogen Synthases

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molecular Plant 2014年第1期7卷 87-100页

作者： Sandra Diaz-Troya Luis lopez-maury Ana maria sanchez-Riego miguel Roldan Francisco J. Florencio Instituto de Bioquimica Vegetal y Fotosintesis Universidad de Sevilla-CSIC Americo Vespucio 49 E-41092 Sevilla Spain

Glycogen constitutes the major carbon storage source in cyanobacteria, as starch in algae and higher plants. Glycogen and starch synthesis is linked to active photosynthesis and both of them are degraded to glucose in the dark to maintain cell metabolism. Control of glycogen biosynthesis in cyanobacteria could be mediated by the regulation of the enzymes involved in this process, ADP-glucose pyrophosphorylase （AGP） and glycogen synthase, which were identified as putative thioredoxin targets. We have analyzed whether both enzymes were subjected to redox modification using purified recombinant enzymes or cell extracts in the model cyanobacterium Synechocystis sp. PCC 6803. Our results indicate that both AGP and glycogen synthases are sensitive to copper oxidation. However, only AGP exhibits a decrease in its enzymatic activity, which is recovered after reduction by DTT or reduced thioredoxin （TrxA）, suggesting a redox control of AGP. In order to elucidate the role in redox control of the cysteine residues present on the AGP sequence （C45, C185, C320, and C337）, they were replaced with serine. All AGP mutant proteins remained active when expressed in Synechocystis, although they showed different electrophoretic mobility profiles after copper oxidation, reflecting a complex pattern of cysteines interaction.

关键词： cyanobacteria glycogen Synechocystis thioredoxin redox regulation.

Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro

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Cellular & molecular Immunology 2018年第10期15卷 917-933页

作者： Jacobo lopez-Abente Adrián Prieto-sanchez maria-Ángeles muñoz-Fernandez Rafael Correa-Rocha marjorie Pion Laboratorio de Inmuno-Regulación Immunology DepartmentPabellón de Medicina y Cirugía ExperimentalHospital General Universitario Gregorio MarañónInstituto de Investigación Sanitaria Gregorio Marañón(IiSGM)Calle Máiquez9Madrid 28009Spain Laboratorio de Inmuno-Biología molecular Immunology DepartmentHospital General Universitario Gregorio MarañónInstituto de Investigación Sanitaria Gregorio Marañón(IiSGM)C/Dr.Esquerdo 46Madrid 28007Spain Networking Research Center on Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)C/Monforte de Lemos 3-5Pabellón 11Madrid 28029Spain

Individuals infected with human immunodeficiency virus type-1(HIV-1)usually show a general dysregulation and hyper-activation of the immune system.A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously ***,the consequences of B-cell dysregulation are still poorly *** evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of *** functionality of treated B cells was challenged in co-culture experiments with autologous CD4+and CD8+T *** demonstrated that HIV-1 induces a phenotypic change in B cells towards a regulatory B-cell phenotype,showing a higher level of IL-10,TGF-β1,EBI3 or IL-12(p35)mRNA expression and acquiring an immunosuppressive *** acquisition of a Breg phenotype was confirmed by co-culture experiments where HIVtreated B cells reduced the proliferation and the TNFαproduction of CD4+or CD8+T *** suppressive ability of HIV-treated B cells was dependent on cell-to-cell contact between these B cells and effector *** our knowledge,these data provide the first evidence that HIV-1 can directly induce a regulatory B cell-like immunosuppressive phenotype,which could have the ability to impair specific immune *** dysregulation could constitute one of the mechanisms underlying unsuccessful efforts to develop an efficient vaccine against HIV-1.

关键词： HIV-1 immune hyper-activation regulatory B cells

Determination of L-norvaline and L-tryptophan in dietary supplements by nano-LC using an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11- dihydroquinidine-silica hybrid monolithic column

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Journal of Pharmaceutical Analysis 2020年第1期10卷 70-77页

作者： Dongsheng Xu Elena sanchez-lopez Qiqin Wang Zhengjin Jiang maría Luisa marina Departamento de Química Analítica Química Física e Ingeniería QuímicaUniversidad de AlcalaCtra.Madrid-Barcelona Km.33.60028871Alcala de Henares(Madrid)Spain Institute of Pharmaceutical Analysis College of PharmacyJinan UniversityGuangzhou510632China Department of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese medicine&New Drug Research Jinan UniversityGuangzhou510632China Instituto de Investigacion Química“Andres m.del Río”(IQAR) Universidad de AlcalaCtra.Madrid-Barcelona Km.33.60028871Alcala de Henares(Madrid)Spain

An analytical methodology based on an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine(mQD)-silica hybrid monolithic column was developed for the enantioseparation of 9-fluorenylmethoxycarbonyl(FmOC)derivatized amino acids by nano-liquid *** mobile phase was optimized including the apparent pH,content of ACN,and concentration of the buffer to obtain a satisfactory enantioresolution performance.27 FmOC derivatized amino acids including 19 protein and 8 non-protein amino acids were tested,and 19 out of them were enantiomerically discriminated obtaining baseline separation for 11 of *** characteristics of the method were evaluated for norvaline and tryptophan in terms of linearity,precision,accuracy,limits of detection(LOD)and quantitation(LOQ)showing good performance to be applied to the enantiomeric determination of these amino acids in dietary *** and LOQ values were 9.3 and 31 mm for norvaline enantiomers and 7.5 and 25 mm for tryptophan enantiomers,*** contents of D-norvaline and D-tryptophan were below their respective LODs in all the analyzed *** of L-tryptophan and L-norvaline showed good agreement with the labeled contents except for one sample which did not show presence of L-norvaline,contrary to the label indication.

关键词： 9-Fluorenylmethoxycarbonyl Amino acids Chiral separation Nano-LC Quinidine-silica hybrid monolithic column