听力与言语-语言病理学

行为科学

医学伦理学

你正在浏览EMBO REPORTS期刊下所有文献
  • Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses.

    abstract::Human immunodeficiency virus 1 (HIV-1) expresses several accessory proteins that manipulate various host-cell processes to achieve optimum replicative efficiency. One of them, viral protein U (Vpu), has been shown to interfere with the cellular degradation machinery through interaction with SCF(beta-TrCP) complexes. T...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor936

    authors: Leulier F,Marchal C,Miletich I,Limbourg-Bouchon B,Benarous R,Lemaitre B

    更新日期:2003-10-01 00:00:00

  • Three-dimensional interplay among the ligand-binding domains of the urokinase-plasminogen-activator-receptor-associated protein, Endo180.

    abstract::Endo180, also known as the urokinase plasminogen activator receptor (uPAR)-associated protein (uPARAP), is one of the four members of the mannose receptor family, and is implicated in extracellular-matrix remodelling through its interactions with collagens, sugars and uPAR. The extracellular portion of Endo180 contain...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor898

    authors: Rivera-Calzada A,Robertson D,MacFadyen JR,Boskovic J,Isacke CM,Llorca O

    更新日期:2003-08-01 00:00:00

  • Effect of CpG methylation on RAG1/RAG2 reactivity: implications of direct and indirect mechanisms for controlling V(D)J cleavage.

    abstract::It has been suggested that DNA methylation/demethylation is involved in regulating V(D)J rearrangement. Although methylated DNA is thought to induce an inaccessible chromatin structure, it is unclear whether DNA methylation can directly control V(D)J recombination independently of chromatin structure. In this study, w...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor904

    authors: Nakase H,Takahama Y,Akamatsu Y

    更新日期:2003-08-01 00:00:00

  • Specific inhibition of gene expression using a stably integrated, inducible small-interfering-RNA vector.

    abstract::We have designed a doxycycline-regulated form of the H1 promoter of RNA polymerase III that allows the inducible knockdown of gene expression by small interfering RNAs (siRNAs). As a proof-of-principle, we have targeted beta-catenin in colorectal cancer (CRC) cells. T-cell factor (TCF) target-gene expression is induce...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor865

    authors: van de Wetering M,Oving I,Muncan V,Pon Fong MT,Brantjes H,van Leenen D,Holstege FC,Brummelkamp TR,Agami R,Clevers H

    更新日期:2003-06-01 00:00:00

  • Widespread PrPSc accumulation in muscles of hamsters orally infected with scrapie.

    abstract::Scrapie, bovine spongiform encephalopathy and chronic wasting disease are orally communicable, transmissible spongiform encephalopathies (TSEs). As zoonotic transmissions of TSE agents may pose a risk to human health, the identification of reservoirs for infectivity in animal tissues and their exclusion from human con...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor827

    authors: Thomzig A,Kratzel C,Lenz G,Krüger D,Beekes M

    更新日期:2003-05-01 00:00:00

  • Phosphorylation of the Stat1 transactivating domain is required for the response to type I interferons.

    abstract::Stat1 (signal transducer and activator of transcription 1) regulates transcription in response to the type I interferons IFN-alpha and IFN-beta, either in its dimerized form or as a subunit of the interferon-stimulated gene factor 3 (Isgf3) complex (consisting of Stat1, Stat2 and interferon-regulating factor 9). Full-...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor802

    authors: Pilz A,Ramsauer K,Heidari H,Leitges M,Kovarik P,Decker T

    更新日期:2003-04-01 00:00:00

  • Differential oxidative damage and expression of stress defence regulons in culturable and non-culturable Escherichia coli cells.

    abstract::Potentially pathogenic bacteria, such as Escherichia coli and Vibrio cholerae, become non-culturable during stasis. The analysis of such cells has been hampered by difficulties in studying bacterial population heterogeneity. Using in situ detection of protein oxidation in single E. coli cells, and using a density-grad...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor799

    authors: Desnues B,Cuny C,Grégori G,Dukan S,Aguilaniu H,Nyström T

    更新日期:2003-04-01 00:00:00

  • The Ark1/Prk1 family of protein kinases. Regulators of endocytosis and the actin skeleton.

    abstract::The Ark/Prk serine/threonine kinases initiate phosphorylation cycles that control the endocytic machinery in mammalian cells and in yeast, and the actin cytoskeleton in yeast. The members of this protein family are unified by homologies in their kinase domain, but are generally diverse in their other domains. The evol...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1038/sj.embor.embor776

    authors: Smythe E,Ayscough KR

    更新日期:2003-03-01 00:00:00

  • Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain.

    abstract::Parkin, a product of the causative gene of autosomal-recessive juvenile parkinsonism (AR-JP), is a RING-type E3 ubiquitin ligase and has an amino-terminal ubiquitin-like (Ubl) domain. Although a single mutation that causes an Arg to Pro substitution at position 42 of the Ubl domain (the Arg 42 mutation) has been ident...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor764

    authors: Sakata E,Yamaguchi Y,Kurimoto E,Kikuchi J,Yokoyama S,Yamada S,Kawahara H,Yokosawa H,Hattori N,Mizuno Y,Tanaka K,Kato K

    更新日期:2003-03-01 00:00:00

  • Priming the nucleosome: a role for HMGB proteins?

    abstract::The high-mobility-group B (HMGB) chromosomal proteins are characterized by the HMG box, a DNA-binding domain that both introduces a tight bend into DNA and binds preferentially to a variety of distorted DNA structures. The HMGB proteins seem to act primarily as architectural facilitators in the manipulation of nucleop...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1038/sj.embor.embor741

    authors: Travers AA

    更新日期:2003-02-01 00:00:00

  • IKCa1 activity is required for cell shrinkage, phosphatidylserine translocation and death in T lymphocyte apoptosis.

    abstract::Apoptotic cell volume decrease (AVD) and exposure of phosphatidylserine (PtdSer) at the cell surface are early events in apoptosis. However, the ion channels responsible for AVD, and their relationship to PtdSer translocation and cell death are poorly understood. Real-time analysis of calcium-induced apoptosis in lymp...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor722

    authors: Elliott JI,Higgins CF

    更新日期:2003-02-01 00:00:00

  • The Gam protein of bacteriophage Mu is an orthologue of eukaryotic Ku.

    abstract::Mu bacteriophage inserts its DNA into the genome of host bacteria and is used as a model for DNA transposition events in other systems. The eukaryotic Ku protein has key roles in DNA repair and in certain transposition events. Here we show that the Gam protein of phage Mu is conserved in bacteria, has sequence homolog...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor709

    authors: d'Adda di Fagagna F,Weller GR,Doherty AJ,Jackson SP

    更新日期:2003-01-01 00:00:00

  • PVF2, a PDGF/VEGF-like growth factor, induces hemocyte proliferation in Drosophila larvae.

    abstract::Blood cells play a crucial role in both morphogenetic and immunological processes in Drosophila, yet the factors regulating their proliferation remain largely unknown. In order to address this question, we raised antibodies against a tumorous blood cell line and identified an antigenic determinant that marks the surfa...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf242

    authors: Munier AI,Doucet D,Perrodou E,Zachary D,Meister M,Hoffmann JA,Janeway CA Jr,Lagueux M

    更新日期:2002-12-01 00:00:00

  • The adenovirus protein Gam1 interferes with sumoylation of histone deacetylase 1.

    abstract::The adenovirus early gene product Gam1 is crucial for virus replication and induces certain cellular genes by inactivating histone deacetylase 1 (HDAC1). We demonstrate that Gam1 (i) destroys promyelocitic leukemia nuclear bodies, (ii) delocalizes SUMO-1 into the cytoplasm and (iii) influences the SUMO-1 pathway. In a...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf213

    authors: Colombo R,Boggio R,Seiser C,Draetta GF,Chiocca S

    更新日期:2002-11-01 00:00:00

  • The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase.

    abstract::CLIP-170/Restin belongs to a family of conserved microtubule (MT)-associated proteins, which are important for MT organization and functions. CLIP-170 is a phosphoprotein and phosphorylation is thought to regulate the binding of CLIP-170 to MTs. However, little is known about the kinase(s) involved. In this study, we ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf197

    authors: Choi JH,Bertram PG,Drenan R,Carvalho J,Zhou HH,Zheng XF

    更新日期:2002-10-01 00:00:00

  • Reverse genetics in the mosquito Anopheles gambiae: targeted disruption of the Defensin gene.

    abstract::Anopheles gambiae, the major vector of human malaria parasite, is an important insect model to study vector-parasite interactions. Here, we developed a simple in vivo double-stranded RNA (dsRNA) knockout approach to determine the function of the mosquito antimicrobial peptide gene Defensin. We injected dsRNA into adul...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf180

    authors: Blandin S,Moita LF,Köcher T,Wilm M,Kafatos FC,Levashina EA

    更新日期:2002-09-01 00:00:00

  • New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae.

    abstract::Streptococcus pneumoniae causes more than one million deaths every year, mostly of young children in developing countries, due to pneumonia, bacteremia and meningitis. The emergence and dissemination of drug-resistant pneumococcal strains, coupled to changing patterns of virulence and the inadequacy of available vacci...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1093/embo-reports/kvf152

    authors: Di Guilmi AM,Dessen A

    更新日期:2002-08-01 00:00:00

  • The Methanobacterium thermoautotrophicum MCM protein can form heptameric rings.

    abstract::Mini-chromosome maintenance (MCM) proteins form a conserved family found in all eukaryotes and are essential for DNA replication. They exist as heteromultimeric complexes containing as many as six different proteins. These complexes are believed to be the replicative helicases, functioning as hexameric rings at replic...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf160

    authors: Yu X,VanLoock MS,Poplawski A,Kelman Z,Xiang T,Tye BK,Egelman EH

    更新日期:2002-08-01 00:00:00

  • Death by necrosis. Uncontrollable catastrophe, or is there order behind the chaos?

    abstract::Cells suffer necrotic death when exposed to extreme environmental conditions, adverse and excessive stimuli, or when deleterious mutations are encoded in their genetic material. Unlike apoptosis, which involves a highly regulated and elaborate network of biochemical events and cascades, necrosis has been considered ge...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf138

    authors: Syntichaki P,Tavernarakis N

    更新日期:2002-07-01 00:00:00

  • Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila.

    abstract::Essential aspects of innate immune responses to microbial infections appear to be conserved between insects and mammals. In particular, in both groups, transmembrane receptors of the Toll superfamily play a crucial role in activating immune defenses. The Drosophila Toll family member 18-Wheeler had been proposed to se...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf130

    authors: Ligoxygakis P,Bulet P,Reichhart JM

    更新日期:2002-07-01 00:00:00

  • Distinct but overlapping domains of AKAP95 are implicated in chromosome condensation and condensin targeting.

    abstract::A-kinase (or PKA)-anchoring protein AKAP95 is a zinc-finger protein implicated in mitotic chromosome condensation by acting as a targeting molecule for the condensin complex. We have identified determinants of chromatin-binding, condensin-targeting and chromosome-condensation activities of AKAP95. Binding of AKAP95 to...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf089

    authors: Eide T,Carlson C,Taskén KA,Hirano T,Taskén K,Collas P

    更新日期:2002-05-01 00:00:00

  • Phosphorylation of histone H3 is functionally linked to retinoic acid receptor beta promoter activation.

    abstract::Ligand-dependent transcriptional activation of retinoic acid receptors (RARs) is a multistep process culminating in the formation of a multimeric co-activator complex on regulated promoters. Several co-activator complexes harbor an acetyl transferase activity, which is required for retinoid-induced transcription of re...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf066

    authors: Lefebvre B,Ozato K,Lefebvre P

    更新日期:2002-04-01 00:00:00

  • Involvement of state transitions in the switch between linear and cyclic electron flow in Chlamydomonas reinhardtii.

    abstract::The energetic metabolism of photosynthetic organisms is profoundly influenced by state transitions and cyclic electron flow around photosystem I. The former involve a reversible redistribution of the light-harvesting antenna between photosystem I and photosystem II and optimize light energy utilization in photosynthes...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf047

    authors: Finazzi G,Rappaport F,Furia A,Fleischmann M,Rochaix JD,Zito F,Forti G

    更新日期:2002-03-01 00:00:00

  • GAAP-1: a transcriptional activator of p53 and IRF-1 possesses pro-apoptotic activity.

    abstract::The mechanisms that regulate the transcription of the tumour suppressor genes p53 and IRF-1 are poorly understood. We have characterized a 68-kDa transcription factor, GAAP-1 (gatekeeper of apoptosis activating proteins), encoded by an alternative splice product of the PRDII-BF1 gene, that recognizes a novel regulator...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf032

    authors: Lallemand C,Palmieri M,Blanchard B,Meritet JF,Tovey MG

    更新日期:2002-02-01 00:00:00

  • The [URE3] phenotype: evidence for a soluble prion in yeast.

    abstract::The aggregation of the two yeast proteins Sup35p and Ure2p is widely accepted as a model for explaining the prion propagation of the phenotypes [PSI+] and [URE3], respectively. Here, we demonstrate that the propagation of [URE3] cannot simply be the consequence of generating large aggregates of Ure2p, because such agg...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvf011

    authors: Fernandez-Bellot E,Guillemet E,Ness F,Baudin-Baillieu A,Ripaud L,Tuite M,Cullin C

    更新日期:2002-01-01 00:00:00

  • Generating patterns from fields of cells. Examples from Drosophila segmentation.

    abstract::In Drosophila, a cascade of maternal, gap, pair-rule and segment polarity genes subdivides the antero/posterior axis of the embryo into repeating segmental stripes. This review summarizes what happens next, i.e. how an intrasegmental pattern is generated and controls the differentiation of specific cell types in the e...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1093/embo-reports/kve255

    authors: Sanson B

    更新日期:2001-12-01 00:00:00

  • Characteristics of post-transcriptional gene silencing.

    abstract::A number of gene silencing phenomena that inactivate genes at the post-transcriptional level have been identified. Due to its potential for studying gene function, post-transcriptional gene silencing (PTGS) has become an intense area of research. In this review we describe the different means of inducing PTGS and disc...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1093/embo-reports/kve231

    authors: Chicas A,Macino G

    更新日期:2001-11-01 00:00:00

  • Yarrowia lipolytica Pex20p, Saccharomyces cerevisiae Pex18p/Pex21p and mammalian Pex5pL fulfil a common function in the early steps of the peroxisomal PTS2 import pathway.

    abstract::Import of peroxisomal matrix proteins is essential for peroxisome biogenesis. Genetic and biochemical studies using a variety of different model systems have led to the discovery of 23 PEX genes required for this process. Although it is generally believed that, in contrast to mitochondria and chloroplasts, translocati...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve228

    authors: Einwächter H,Sowinski S,Kunau WH,Schliebs W

    更新日期:2001-11-01 00:00:00

  • Dynactin-membrane interaction is regulated by the C-terminal domains of p150(Glued).

    abstract::Dynactin has been proposed to link the microtubule-associated motor cytoplasmic dynein with membranous cargo; however, the mechanism by which dynactin-membrane interaction is regulated is unknown. Here we show that dynein and dynactin exist in discrete cytosolic and membrane-bound states in the filamentous fungus Neur...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve202

    authors: Kumar S,Zhou Y,Plamann M

    更新日期:2001-10-01 00:00:00

  • Estrogen receptors: orchestrators of pleiotropic cellular responses.

    abstract::Estrogen receptors (ERs) orchestrate both transcriptional and non-genomic functions in response to estrogens, xenoestrogens and signals emanating from growth factor signalling pathways. The pleiotropic and tissue-specific effects of estrogens are likely to be mediated by the differential expression of distinct estroge...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1093/embo-reports/kve185

    authors: Moggs JG,Orphanides G

    更新日期:2001-09-01 00:00:00

  • A novel muscle LIM-only protein is generated from the paxillin gene locus in Drosophila.

    abstract::Paxillin is a protein containing four LIM domains, and functions in integrin signaling. We report here that two transcripts are generated from the paxillin gene locus in Drosophila; one encodes a protein homolog of the vertebrate Paxillin (DPxn37), and the other a protein with only three LIM domains, partly encoded by...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve178

    authors: Yagi R,Ishimaru S,Yano H,Gaul U,Hanafusa H,Sabe H

    更新日期:2001-09-01 00:00:00

  • Sex and sugar in yeast: two distinct GPCR systems.

    abstract::Although eukaryotic G-protein coupled receptor (GPCR) systems are well known for their ability to detect and mediate rapid responses to extracellular signals, the full range of stimuli to which they respond may not yet have been identified. Activation of GPCRs by hormones, pheromones, odorants, neurotransmitters, ligh...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1093/embo-reports/kve132

    authors: Versele M,Lemaire K,Thevelein JM

    更新日期:2001-07-01 00:00:00

  • The solution structure of PapGII from uropathogenic Escherichia coli and its recognition of glycolipid receptors.

    abstract::Uropathogenic Escherichia coli (UPEC) is the primary cause of symptomatic urinary tract infection. The P-pili, a bacterial surface organelle, mediates the bacterial host--cell adhesion. The PapG adhesin has generated much interest in recent years, not only because of its clinical value, i.e. in the prevention of micro...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve133

    authors: Sung MA,Fleming K,Chen HA,Matthews S

    更新日期:2001-07-01 00:00:00

  • Secured cutting: controlling separase at the metaphase to anaphase transition.

    abstract::The final irreversible step in the duplication and distribution of genomes to daughter cells takes place at the metaphase to anaphase transition. At this point aligned sister chromatid pairs split and separate. During metaphase, cohesion between sister chromatids is maintained by the chromosomal multi-subunit cohesin ...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1093/embo-reports/kve113

    authors: Uhlmann F

    更新日期:2001-06-01 00:00:00

  • Introns and their positions affect the translational activity of mRNA in plant cells.

    abstract::In an attempt to further increase transgene expression levels in plants over and above the enhancement obtained with a 5' untranslated leader intron, three different maize introns were inserted at three different positions within the coding sequence of the luciferase reporter gene. Constructs were transformed into mai...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve090

    authors: Bourdon V,Harvey A,Lonsdale DM

    更新日期:2001-05-01 00:00:00

  • Direct competition between Brinker and Drosophila Mad in Dpp target gene transcription.

    abstract::Brinker is a nuclear protein that antagonizes Dpp signalling in Drosophila. Its expression is negatively regulated by Dpp. Here, we show that Brinker represses Ultrabithorax (Ubx) in the embryonic midgut, a HOX gene that activates, and responds to, the localized expression of Dpp during endoderm induction. We find tha...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve068

    authors: Saller E,Bienz M

    更新日期:2001-04-01 00:00:00

  • Telomerase subunit overexpression suppresses telomere-specific checkpoint activation in the yeast yku80 mutant.

    abstract::Ku is a conserved heterodimeric DNA-binding protein that plays critical roles in DNA repair and telomere homeostasis. In Saccharomyces cerevisiae, deletion of YKU70 or YKU80 results in an inability to grow at 37 degrees C. This is suppressed by overexpression of several components of telomerase (EST1, EST2 and TLC1). ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve038

    authors: Teo SH,Jackson SP

    更新日期:2001-03-01 00:00:00

  • Molecular and cytological analysis of a 5.5 Mb minichromosome.

    abstract::Mammalian artificial chromosomes (MACs) provide a new tool for the improvement of our knowledge of chromosome structure and function. Moreover, they constitute an alternative and potentially powerful tool for gene delivery both in cultured cells and for the production of transgenic animals. In the present work we desc...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve018

    authors: Auriche C,Donini P,Ascenzioni F

    更新日期:2001-02-01 00:00:00

  • p21cip1 is required for the differentiation of oligodendrocytes independently of cell cycle withdrawal.

    abstract::Differentiation of most cell types requires both establishment of G1 arrest and the induction of a program related to achieving quiescence. We have chosen to study the differentiation of oligodendrocyte cells to determine the role of p27 and p21 in this process. Here we report that both p27 and p21 are required for th...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve008

    authors: Zezula J,Casaccia-Bonnefil P,Ezhevsky SA,Osterhout DJ,Levine JM,Dowdy SF,Chao MV,Koff A

    更新日期:2001-01-01 00:00:00

  • Limiting DNA replication to once and only once.

    abstract::In Escherichia coli cells, the origin of chromosomal replication is temporarily inactivated after initiation has occurred. Origin sequestration is the first line of defence against over-initiation, providing a time window during which the initiation potential can be reduced by: (i) titration of DnaA proteins to newly ...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1093/embo-reports/kvd116

    authors: Boye E,Løbner-Olesen A,Skarstad K

    更新日期:2000-12-01 00:00:00

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