Abstract:
:Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b+ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Mosca F,Tritto E,Muzzi A,Monaci E,Bagnoli F,Iavarone C,O'Hagan D,Rappuoli R,De Gregorio Edoi
10.1073/pnas.0804699105subject
Has Abstractpub_date
2008-07-29 00:00:00pages
10501-6issue
30eissn
0027-8424issn
1091-6490pii
0804699105journal_volume
105pub_type
杂志文章abstract::The method of matrix isolation has been used to investigate mechanisms of gas-phase chemical reactions, in particular the pyrolysis of some organomercury compounds. A molecular beam of pyrolysis products was condensed simultaneously with a large excess of rare gas at temperatures from 5 to 15 degrees K to form a matri...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.12.3238
更新日期:1971-12-01 00:00:00
abstract::R. A. Fisher's 1930 "reproductive value" is defined as the contribution made by a population's initial age elements to its asymptotically dominating exponential growth mode. For the Leslie discrete-time model, it is the characteristic row vector of the Leslie matrix, and for the integral-equation model of Lotka the si...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.11.5189
更新日期:1977-11-01 00:00:00
abstract::Mature peripheral T cells respond to foreign but not to self-antigens. During development in the thymus, deletion of high-affinity self-reactive immature thymocytes contributes to tolerance of mature T cells. However, double-positive thymocytes are positively selected to survive if they respond to self-peptide-MHC com...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1119272109
更新日期:2012-05-08 00:00:00
abstract::Double-stranded DNA break repair by homologous recombination is initiated by resection of free DNA ends to produce a 3'-ssDNA overhang. In bacteria, this reaction is catalyzed by helicase-nuclease complexes such as AddAB in a manner regulated by specific recombination hotspot sequences called Crossover hotspot instiga...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1303035110
更新日期:2013-07-09 00:00:00
abstract::A model for protein synthesis is proposed in which the donor for the peptide elongation reaction is peptidyl-5S RNA. Space-filling models show that peptide bond formation between peptidyl-5S RNA and aminoacyl-tRNA is eminently feasible from a stereochemical point of view. The peptide is transferred to 5S RNA, while at...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.10.2357
更新日期:1971-10-01 00:00:00
abstract::Under particular circumstances like lactation and fasting, the blood-borne monocarboxylates acetoacetate, beta-hydroxybutyrate, and lactate represent significant energy substrates for the brain. Their utilization is dependent on a transport system present on both endothelial cells forming the blood-brain barrier and o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.7.3990
更新日期:1998-03-31 00:00:00
abstract::Insulin and insulin-like growth factor 1 (IGF1) are ubiquitous growth factors that regulate proliferation in most mammalian tissues including pancreatic islets. To explore the specificity of insulin receptors in compensatory beta-cell growth, we examined two models of insulin resistance. In the first model, we used li...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0608703104
更新日期:2007-05-22 00:00:00
abstract::We describe here the 1.7-A resolution structure of a single-chain antibody variable domain (scFv) molecule, based on the carbohydrate-binding antibody Se155-4, complexed with the trisaccharide ligand alpha-D-Gal(1-->2)[alpha-D-Abe(1-->3)]alpha-D-Manp1-->OMe, where Abe is abequose. The scFv expressed in Escherichia col...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.14.6423
更新日期:1994-07-05 00:00:00
abstract::Calendar date of the beginning of the growing season at high altitude in the Colorado Rocky Mountains is variable but has not changed significantly over the past 25 years. This result differs from growing evidence from low altitudes that climate change is resulting in a longer growing season, earlier migrations, and e...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.4.1630
更新日期:2000-02-15 00:00:00
abstract::Covariance analysis of protein sequence alignments uses coevolving pairs of sequence positions to predict features of protein structure and function. However, current methods ignore the phylogenetic relationships between sequences, potentially corrupting the identification of covarying positions. Here, we use random m...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1711913115
更新日期:2018-01-23 00:00:00
abstract::During cytokinesis, a cleavage furrow generated by actomyosin ring contraction is restructured into the midbody, a platform for the assembly of the abscission machinery that controls the final separation of daughter cells. The polymerization state of F-actin is important during assembly, ingression, disassembly, and c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1722281115
更新日期:2018-02-27 00:00:00
abstract::Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.122225399
更新日期:2002-07-23 00:00:00
abstract::Ribozyme activity in vivo depends on achieving high-level expression, intracellular stability, target colocalization, and cleavage site access. At present, target site selection is problematic because of unforeseeable secondary and tertiary RNA structures that prevent cleavage. To overcome this design obstacle, we wis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.091411398
更新日期:2001-05-08 00:00:00
abstract::Bacteriophage lambda encodes a number of genes involved in the recombinational repair of DNA double-strand breaks. The product of one of these genes, rap, has been purified. Truncated Rap proteins that copurify with the full-length form are derived, at least in part, from a rho-dependent transcription terminator locat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.23.13507
更新日期:1998-11-10 00:00:00
abstract::Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0504343102
更新日期:2005-12-20 00:00:00
abstract::Stomatal pores are microscopic structures on the epidermis of leaves formed by 2 specialized guard cells that control the exchange of water vapor and CO(2) between plants and the atmosphere. Stomatal size (S) and density (D) determine maximum leaf diffusive (stomatal) conductance of CO(2) (g(c(max))) to sites of assim...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0904209106
更新日期:2009-06-23 00:00:00
abstract::Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1510493113
更新日期:2016-07-05 00:00:00
abstract::Biological diversity reflects an underlying molecular diversity. The molecules found in nature may be regarded as solutions to challenges that have been confronted and overcome during molecular evolution. As our understanding of these solutions deepens, the efficiency with which we can discover and/or design new treat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.92.1.75
更新日期:1995-01-03 00:00:00
abstract::The specific nucleocytoplasmic compartmentalization of proteins has been examined for some major soluble acidic nuclear proteins in oocytes of different amphibia. Proteins synthesized and radioactively labeled by translation in vitro, by using mRNA from ovaries of the frog Xenopus laevis, were injected into the cytopl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.17.5302
更新日期:1982-09-01 00:00:00
abstract::The mechanism by which mammalian cells acquire resistance to chemotherapeutic agents has been investigated by using molecular genetic techniques. LZ and C5, two independently derived multidrug-resistant Chinese hamster cell lines, share specific amplified DNA sequences. We demonstrate that commonly amplified DNA seque...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.2.337
更新日期:1986-01-01 00:00:00
abstract::Modulation of cholesterol absorption in the intestine, the primary site of dietary cholesterol uptake in humans, can have profound clinical implications. We have undertaken a reverse genetic approach by disrupting putative cholesterol processing genes in zebrafish larvae by using morpholino (MO) antisense oligonucleot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,收录出版
doi:10.1073/pnas.0400441101
更新日期:2004-03-09 00:00:00
abstract::Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflam...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1306621110
更新日期:2013-10-01 00:00:00
abstract::The rat W3/25 antigen was the first marker antigen of helper T lymphocytes to be identified. Subsequently, the human OKT4 antigen (now called CD4) was described, and cell distribution and functional data suggested that W3/25 and OKT4 antigens were homologous. This is now confirmed by the matching of peptide sequences ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.6.1649
更新日期:1987-03-01 00:00:00
abstract::Dispersed cell cultures were established from 7- to 9-day postnatal mouse cerebellum. The fibrin slice method was used to obtain a localization of plasminogen activator production to specific cells. Fibrinolytically active cells were small (5- to 8-micrometer diameter), round, and occurred singly or in aggregates. Fib...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.12.7810
更新日期:1981-12-01 00:00:00
abstract::The c-rings of ATP synthases consist of individual c-subunits, all of which harbor a conserved motif of repetitive glycine residues (GxGxGxG) important for tight transmembrane α-helix packing. The c-ring stoichiometry determines the number of ions transferred during enzyme operation and has a direct impact on the ion-...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1303333110
更新日期:2013-05-07 00:00:00
abstract::Soluble, glutathione-stimulated delta 5-3-ketosteroid isomerase (EC 5.3.3.A) activity of human and rat liver resides in very basic proteins with molecular weights of about 45,000 which are present in high concentrations in these tissues. Physiochemical and immunological evidence is presented for the identity of the pr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.1.158
更新日期:1977-01-01 00:00:00
abstract::Posttranslational modification is an important element in circadian clock function from cyanobacteria through plants and mammals. For example, a number of key clock components are phosphorylated and thereby marked for subsequent ubiquitination and degradation. Through forward genetic analysis we demonstrate that prote...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1011987107
更新日期:2010-12-07 00:00:00
abstract::A comparison of five constant region sequences of human and mouse k and lambda immunoglobulin chains has been undertaken in order to reveal sequence homologies and evolutionary relationships. Simultaneously, a comparison with the three-dimensional structure of one mouse k-chain (McPC 603) has suggested structural reas...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.7.2785
更新日期:1975-07-01 00:00:00
abstract::IL-17-producing CD4(+) T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-beta, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor RORgammat. The maintenance, ex...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900408106
更新日期:2009-03-24 00:00:00
abstract::Mutations in the human DYNC1H1 gene are associated with neurological diseases. DYNC1H1 encodes the heavy chain of cytoplasmic dynein-1, a 1.4-MDa motor complex that traffics organelles, vesicles, and macromolecules toward microtubule minus ends. The effects of the DYNC1H1 mutations on dynein motility, and consequently...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1620141114
更新日期:2017-02-28 00:00:00