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sIRT3-mediated inhibition of FOs through histone H3 deacetylation prevents cardiac fibrosis and inflammation

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signal Transduction and Targeted Therapy 2020年第1期5卷 2322-2331页

作者： Xavier Palomer Msilvia Román-Azcona javier Pizarro-Delgado Ana Planavila Francesc villarroya Brenda valenzuela-Alcaraz Fátima Crispi Álvaro sepúlveda-martínez Irene Miguel-Escalada Jorge Ferrer JFrancisco Nistal Raquel García Mercy MDavidson Emma Barroso manuel vázquez-Carrera Department of Pharmacology Toxicology and Therapeutic ChemistryIBUB(Institut de Biomedicina de la Universitat de Barcelona)Research Institute-Pediatric Research InstituteHospital Sant Joan de Déuand CIBER de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM)Faculty of Pharmacy and Food SciencesUniversity of BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Biomedicine IBUB and CIBER Fisiopatología de la Obesidad y Nutrición(CIBEROBN)Faculty of BiologyUniversity of BarcelonaBarcelonaSpain aBCNatal-Barcelona Center for Maternal–Fetal and Neonatal Medicine(Hospital Clínic and Hospital sant Joan de Deu) Institut d’Investigacions Biomèdiques August Pi i SunyerUniversitat de Barcelonaand Center for Biomedical Research on Rare Diseases(CIBER-ER)BarcelonaSpain Genomic Programming of Betacells Laboratory Institut d’Investigacions August Pi i Sunyer(IDIBAPS)and CIBERDEMBarcelonaSpain section of Epigenomics and Disease Department of Medicineand National Institute for Health Research(NIHR)Imperial Biomedical Research CentreImperial College LondonLondonUK servicio de Cirugía Cardiovascular Hospital Universitario Marqués de ValdecillaDepartamento de Ciencias Médicas y QuirúrgicasFacultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)Centro de Investigación Biomédica en Red Cardiovascular(CIBERCV)Instituto de Salud Carlos IIISantanderSpain Departamento de Fisiología y farmacología Facultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)SantanderSpain Department of Radiation Oncology Columbia UniversityNew YorkNYUSA

sirtuin 3(sIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative *** of sIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac *** this study,we investigated the role of sIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of sIRT3 and human cardiac AC16 ***3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of *** with this,sIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOs and the DNA-binding activity of ***,we demonstrated that sIRT3 inhibits FOs transcription through specific histone H3 lysine K27 deacetylation at its *** findings highlight an important function of sIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOs/AP-1 *** fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to sIRT3 as a potential target for treating these diseases.

关键词： sIRT3 inflammation cardiac

The study of Carbamoyl Phosphate synthetase 1 Deficiency sheds Light on the Mechanism for switching On/Off the Urea Cycle

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Journal of Genetics and Genomics 2015年第5期42卷 249-260页

作者： Carmen Díez-Fernández josé Gallego Johannes H?berle javier Cervera vicente Rubio Institute for Biomedicine of valencia of the spanish Research Council Medical school of the Catholic University of valencia University Children's Hospital Zurich and Children's Research Center Centre for Biomedical Networking Research on Rare Diseases of the Carlos Ⅲ Health Institute

Carbamoyl phosphate synthetase i （CPs1） deficiency （CPs1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPs1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPs1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPs 1, N-acetyl- L-glutamate （NAG）, is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPs1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L- glutamate （a registered drug, the analog of NAG）. Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the 134-~4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPs1.

关键词： Urea cycle diseases Inborn errors Hyperammonemia site-directed mutagenesis Restrained molecular dynamics Allosteric regulation Carbamoyl phosphate synthetase 1 Enzyme

Different Thermostability of skeletal Muscle Glyceraldehyde-3-phosphate Dehydrogenase from Hibernating and Euthermic Jerboa (Jaculus orientalis)

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Acta Biochimica et Biophysica sinica 2003年第10期35卷 891-896页

作者： IDDAR Abdelghani,CAMPOs Luis A.,sancho javier,sERRANO Aurelio,sOUKRI Abdelaziz Laboratoire de Biochimie Departamento de Bioquímica y Biología Molecular y Celular Departamento de Bioquímica y Biología Molecular y Celular Instituto de Bioquímica vegetal y Fotosíntesis Laboratoire de Biochimie Unitè de Gènie Enzymatique et Biologie Molèculaire facultè des sciences-Ain Chock Casablanca Morocco Universidad de Zaragoza Zaragoza spain Universidad de Zaragoza Zaragoza spain CsIC-Universidad de sevilla sevilla spain Unitè de Gènie Enzymatique et Biologie Molèculaire facultè des sciences-Ain Chock Casablanca Morocco

In previous study, we demonstrated that the specific activity of D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.***.1.12) in skeletal muscle of induced hibernating jerboa (hibernating GAPDH) was 3-4 folds lower than that of the one in the skeletal muscle of the euthermic jerboa (euthermic GAPDH). A significant decrease in both GAPDH protein and GapC mRNA levels occurs when hibernating, but the purified hibernating GAPDH is less active than the euthermic GAPDH. To investigate the physico-chemical basis of this lower activity, the behaviour during thermal inactivation of skeletal muscle GAPDH from hibernating and euthermic tissues was examined by a variety of spectroscopic techniques, including fluorescence emission, circular dichroism and ultraviolet absorption. A clear resistance to thermal denaturation was observed in the hibernating GAPDH compared with the euthermic GAPDH. The different temperature of denaturation found in these proteins by both fluorimetry and circular dichroism indicates that there might exist conformational changes of GAPDH upon hibernation that could affect the stability of this enzyme.

关键词： glyceraldehyde-3-phosphate dehydrogenase hibernation thermal denaturation circular dichroism spectroscopy protein stability

Enhancement of the benthic communities around an isolated island in the Antarctic Ocean

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Acta Oceanologica sinica 2013年第6期32卷 47-55页

作者： josé I saiz Nuria Anadón javier Cristobo Oscar García-Alvarez Gerardo García-Castrillo Eduardo López Cruz Palacín Jesús s Troncoso Ana Ramos Department of Zoology and Animal Cell Biology University of the Basque CountryBilbao 48080 Spain Department of Organisms and systems Biology (Zoology) Rodrigo Uría s/n University of OviedoOviedo 33071 Spain spanish Institute of Oceanography Gijón Oceanographic Centre Príncipe de Asturias 70bisGijón 33212 Spain Department of Zoology and Physical Anthropology University of Santiago de CompostelaSouth Campus Santiago de Compostela 15706 Spain Cantabrian maritime Museum San Martín de Bajamar s/nSantander 39004 Spain Department of Biology Faculty of Sciences Autonomous University of MadridMadrid 28049 Spain Department of Animal Biology University of BarcelonaAvinguda Diagonal 645 Barcelona 08028 Spain Department of Ecology and Animal Biology Marine Sciences Faculty University of VigoVigo 36310 Spain spanish Institute of Oceanography Subida a Radio Faro 50-52Vigo 36390 Spain

Insular marine biotas are often richer in faunal diversity than those from the open sea in the same geo- graphical region. The existence of particular island effects were tested under polar conditions by compar- ing infaunal benthic assemblages on Peter I Island with those of similar latitudes in the open ocean at the Bellingshausen sea and also from the coast of the Antarctic Peninsula. sampling was carried out aboard the R/v Hesperides during the expedition named BENTART-2003 from 24 January to 3 march 2003. Benthic samples were collected at 18 stations ranging from 90 to 2 044 m depth, using an UsNEL-type box corer （BC） dredge. Representatives of 32 higher taxa of invertebrates were found. Univariate and multivariate analyses revealed various patterns in the data. First, significant differences in polychaete abundance were detected between the stations located in the open sea and the remaining sites （island plus mainland sites）. Bivalve abundances were also distinct between island and mainland sampling sites. sediment columns taken from the island seafloor exhibited the highest rate of bioturbation by the infauna. These findings confirm the model that islands develop distinct assemblages characterized by the enhancement of the benthic commu- nities even in cold waters. several abiotic factors were measured simultaneously at the seafloor and along the water column to investigate faunal distribution patterns. significant correlations were found between the benthic assemblages and a combination of two environmental variables：＂island effect＂（measured as a categorical variable） and the redox state of sediments. Richer and more complex benthic assemblages were found in Peter I Island＇s sea bottom, whereas the more depauperate bottoms remained in the open sea.

关键词： Antarctica Bellingshausen sea benthos Peter I Island PRIMER

The Quaternary structure of NADPH Thioredoxin Reductase C Is Redox-sensitive

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Molecular Plant 2009年第3期2卷 457-467页

作者： Juan manuel Pérez-Ruiz maricruz Gonzalez maria Cristina spinola Luisa maria sandalio Francisco javier Cejudo Instituto de Bioqulmica vegetal y Fotoslntesis Universidad de Sevilla y CSIC Avda Américo Vespucio 49 41092-Sevilla Spain Present address: Plant Biology Laboratory The Salk Institute 10010 N. Torrey Pines Rd La Jolla CA 92037 USA Estacion Experimental del Zaidin CSIC C/Prof Albareda 1 18008-Granada Spain

NADPH thioredoxin reductase C （NTRC） is a chloroplast enzyme able to conjugate NADPH thioredoxin reductase （NTR） and thioredoxin （TRX） activities for the efficient reduction of 2-Cys peroxiredoxin （2-Cys PRX）. Because NADPH can be produced in chloroplasts during darkness, NTRC plays a key role for plant peroxide detoxification during the night. Here, it is shown that the quaternary structure of NTRC is highly dependent on its redox status. In vitro, most of the enzyme adopted an oligomeric state that disaggregated in dimers upon addition of NADPH, NADH, or DTT. Gel filtration and Western blot analysis of protein extracts from Arabidopsis chloroplast stroma showed that native NTRC forms aggregates, which are sensitive to NADPH and DTT, suggesting that the aggregation state might be a significant aspect of NTRC activity in vivo. Moreover, the enzyme is localized in clusters in Arabidopsis chloroplasts. NTRC triple and double mutants, A164G- v182E-R183F and A164G-R183F, replacing key residues of NADPH binding site, showed reduced activity but were still able to dimerize though with an increase in intermediary forms. Based on these results, we propose that the catalytically active form of NTRC is the dimer, which formation is induced by NADPH.

关键词： Abiotic/environmental stress oxidative and photo-oxidative stress photosynthesis Arabidopsis rice.

Education-based approach to addressing non-evidence-based practice in preventing NsAID-associated gastrointestinal complications

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World Journal of Gastroenterology 2009年第47期15卷 5953-5959页

作者： Angel Lanas Juan v Esplugues javier Zapardiel Eduardo sobreviela service of Digestive Diseases University Hospital University of ZaragozaInstituto Aragonés de Ciencias de la Salud(IACS)Centros de Investigación en Red de Enfermedades Hepáticas y Digestivas(CIBERehd)C/San Juan Bosco 15 50009 ZaragozaSpain Department of Pharmacology University of ValenciaCIBERehdAv.Vicent Andrés Estellés s/n46100 BurjassotValenciaSpain Department of Medical AstraZeneca Farmacéutica SpainParque NorteEdificio RobleC/Serrano Galvache 5628033 MadridSpain MediClin-Quintiles c/Sardenya no 541-54308024 BarcelonaSpain

AIM:To evaluate an evidence-based educational program for improving strategies for prevention of non-steroidal anti-inflammatory drug(NsAID)-associated gastrointestinal(GI)complications. METHODs:Four hundred and fifty-six specialists replied to a questionnaire that covered issues related to NsAID-induced adverse *** also collected data from their last five consecutive patients before and after they had attended an evidence-based seminar on GI prevention strategies. REsULTs:Four hundred and forty-one of 456 specialists(96.7%)participated in the survey,and 382(83.7%)in the education-based study that recorded data from 3728 *** specialists overestimated the risk of GI complications with NsAIDs,underestimated the GI safety profile of coxibs,but were aware of the risk factors and of the current prevention *** pump inhibitors were co-prescribed with NsAIDs in>80% of patients with and without risk *** educational program had little impact on prescribing ***:specialists are informed of advances in NsAID-associated adverse effects and have high rates of GI-prevention *** educational program did not alter these rates.

关键词： Nonsteroidal anti-inflammatory agents Education Gastrointestinal diseases Adverse effects Cyclooxygenase 2 inhibitors Proton pump inhibitors

Modeling of the Water Table Level Response Due to Extraordinary Precipitation Events: The Case of the Guadalupe valley Aquifer

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International Journal of Geosciences 2013年第6期4卷 950-958页

作者： javier González Ramírez Rogelio vázquez González Earth sciences Division Center for Scientific Research and Higher Education at Ensenada Ensenada Mexico

A two-dimensional algorithm for underground water flow simulation was modified and adapted to the geohydrologic conditions of the Guadalupe valley located in the state of Baja California in northern México. In order to solve the numerical model using the balance equation, the central finite differences with spatial and temporal constant increments method were used. such model considers a heterogeneous and transient unconfined aquifer. Modeling and calibration processes are presented using the data of water table levels provided by the water level data loggers installed in a monitoring network and precipitation data from climatic stations of both seasons: 2009-2010 and 2010-2011. It was possible to locate, correlate and model specific rainfall-recharge events with the aim of obtaining an estimation of how these events are directly reflected on the water table level of the aquifer and how it reacts against simulated extraordinary events.

关键词： Geohydrologic Model Precipitation Recharge Finite Differences Method

Multi-gigahertz mode-locked femtosecond Yb:KLuW waveguide lasers

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Photonics Research 2022年第11期10卷 2584-2589页

作者： JI EUN BAE XAvIER MATEOs MAGDALENA AGUILÓ FRANCEsC DÍAZ javier GARCÍA AJATEs CAROLINA ROMERO javier RODRÍGUEZ vÁzquez DE ALDANA faBIAN ROTERMUND Department of Physics Korea Advanced Institute of Science and Technology(KAIST)34141 DaejeonRepublic of Korea Universitat Rovira i virgili(URv) Fı´sica i Cristal·lografia de Materials i Nanomaterials(FiCMA)43007 TarragonaSpain Grupo de Investigación en Aplicaciones del Láser y Fotónica University of Salamanca37008 SalamancaSpain

We demonstrate multi-gigahertz continuous-wave mode-locking of a Yb:KLuW waveguide laser. A femtosecondlaser-inscribed Yb:KLuW channel waveguide in an extended laser cavity delivers a fundamentally mode-locked laser near 1030 nm. A tunable few-centimeter-long cavity containing a single-walled carbon nanotube saturable absorber as mode-locker generates self-starting femtosecond pulses with average output powers exceeding210 mW at repetition rates of 2.27, 2.69, and 3.55 GHz. The laser cavity, which includes a wedged waveguide,is extended by using a lens pair that controls the laser fluence on the saturable absorber for reliable mode-locked operation without instability. The presented laser performance, mode-locked up to 3.55 GHz, highly suggests the potential of crystalline Yb:KLuW waveguides for realizing high-power ultrafast lasers with higher GHz repetition rates in a quasi-monolithic cavity.

关键词： waveguide femtosecond mode

Mid-infrared waveguiding in three-dimensional microstructured optical waveguides fabricated by femtosecond-laser writing and phosphoric acid etching

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Photonics Research 2020年第3期8卷 257-262页

作者： JINMAN Lv BINBIN HONG YANG TAN FENG CHEN javier RODRíGUEZ vázquez DE ALDANA GUO PING WANG Institute of Microscale Optoelectronics Shenzhen UniversityShenzhen 518052China school of Physics State Key Laboratory of Crystal MaterialsShandong UniversityJinan 250100China Departamento Fisica Aplicada Facultad CienciasUniversidad de SalamancaSalamanca 37008Spain

We fabricated a three-dimensional microstructured optical waveguide(MOW)in a single-crystal using femtosecond-laser writing and phosphoric acid etching techniques,and observed excellent midinfrared waveguiding performance with low loss of^0.5 d B∕*** with a periodic arrangement were written inside the yttrium aluminum garnet(YAG)crystal via femtosecond laser inscription,and then etched by the phosphoric acid(H3 PO4)to form hollow *** evolution of the microstructure of tracks was investigated in *** function of the MOW was analyzed by different numerical methods,indicating the proposed MOW can effectively operate in quasi-single-mode pattern in the midinfrared wavelength range,which agrees well with our experiment results.

关键词： microstructure laser wave