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111.
Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines 总被引:2,自引:0,他引:2
Carralot JP Probst J Hoerr I Scheel B Teufel R Jung G Rammensee HG Pascolo S 《Cellular and molecular life sciences : CMLS》2004,61(18):2418-2424
In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based
vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to
any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled
expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies).
We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for
-galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy
primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application
of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the
administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the
requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004 相似文献
112.
113.
Telomere length in humans is partly controlled by a feedback mechanism in which telomere elongation by telomerase is limited by the accumulation of the TRF1 complex at chromosome ends. TRF1 itself can be inhibited by the poly(ADP-ribose) polymerase (PARP) activity of its interacting partner tankyrase 1, which abolishes its DNA binding activity in vitro and removes the TRF1 complex from telomeres in vivo. Here we report that the inhibition of TRF1 by tankyrase is in turn controlled by a second TRF1-interacting factor, TIN2 (ref. 6). Partial knockdown of TIN2 by small hairpin RNA in a telomerase-positive cell line resulted in telomere elongation, which is typical of reduced TRF1 function. Transient inhibition of TIN2 with small interfering RNA led to diminished telomeric TRF1 signals. This effect could be reversed with the PARP inhibitor 3-aminobenzamide and did not occur in cells overexpressing a PARP-dead mutant of tankyrase 1. TIN2 formed a ternary complex with TRF1 and tankyrase 1 and stabilized their interaction, an effect also observed with the PARP-dead mutant of tankyrase 1. In vitro, TIN2 protected TRF1 from poly(ADP-ribosyl)ation by tankyrase 1 without affecting tankyrase 1 automodification. These data identify TIN2 as a PARP modulator in the TRF1 complex and can explain how TIN2 contributes to the regulation of telomere length. 相似文献
114.
An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice 总被引:19,自引:0,他引:19
Roy CN Custodio AO de Graaf J Schneider S Akpan I Montross LK Sanchez M Gaudino A Hentze MW Andrews NC Muckenthaler MU 《Nature genetics》2004,36(5):481-485
Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron retention, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this 'iron withholding' reduces the iron available to maturing red blood cells and eventually contributes to the development of anemia. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone that inhibits duodenal iron absorption and macrophage iron release. Hamp is part of the type II acute phase response and is thought to have a crucial regulatory role in sequestering iron in the context of ACD. Mice with deficiencies in the hemochromatosis gene product, Hfe, mounted a general inflammatory response after injection of lipopolysaccharide but lacked appropriate Hamp expression and did not develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD. 相似文献
115.
Vissers LE van Ravenswaaij CM Admiraal R Hurst JA de Vries BB Janssen IM van der Vliet WA Huys EH de Jong PJ Hamel BC Schoenmakers EF Brunner HG Veltman JA van Kessel AG 《Nature genetics》2004,36(9):955-957
CHARGE syndrome is a common cause of congenital anomalies affecting several tissues in a nonrandom fashion. We report a 2.3-Mb de novo overlapping microdeletion on chromosome 8q12 identified by array comparative genomic hybridization in two individuals with CHARGE syndrome. Sequence analysis of genes located in this region detected mutations in the gene CHD7 in 10 of 17 individuals with CHARGE syndrome without microdeletions, accounting for the disease in most affected individuals. 相似文献
116.
117.
Riassunto È stato dimostrato che la transulfurazione che consegue alla incubazione dei solfinati con zolfo ed un composto tiolico è dovuta in parte alla produzione di un polisolfuro organico, formato dal tiolo e zolfo, ed in parte al polisolfuro inorganico, formato dalla decomposizione di quello organico. L'entità della transulfurazione prodotta direttamente dal polisolfuro organico varia con il tipo di polisolfuro e dipende dalla sua stabilità nelle condizioni usate. 相似文献
118.
Riassunto Si descrivono gli effetti teratogeni indotti nella coda del girino delBufo arenarum in uno stadio premetamorfosico, come conseguenza dell'impianto di cristalli di idrocarburi cancerigeni. Tanto il MC come il BP o il DMBA producono alette sopranumerarie che ripetono le strutture istologiche delle alette normali; ed inoltre il DMBA induce la formazione di una seconda notocorda parallela alla normale.
Career investigator of Argentine CNICT.
Fellow of Argentine CNICT. 相似文献
Career investigator of Argentine CNICT.
Fellow of Argentine CNICT. 相似文献
119.
Summary Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.This investigation was supported by Consejo de Desarrollo Científico y Humanístico de la Universidad del Zulia, and by CONICIT Grant S1-0455. 相似文献
120.