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::Newly translated tubulin molecules undergo a series of complex interactions with nascent chain-binding chaperones, including prefoldin (PFD) and chaperonin-containing TCP-1 (CCT). By screening for oryzalin hypersensitivity, we identified several mutants of Arabidopsis that have lesions in PFD subunits. The pfd6-1 muta...
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.0808652105
更新日期:2008-11-18 00:00:00
abstract::Although normal fatty acids (FAs) are degraded via β-oxidation, unusual FAs such as 2-hydroxy (2-OH) FAs and 3-methyl-branched FAs are degraded via α-oxidation. Phytosphingosine (PHS) is one of the long-chain bases (the sphingolipid components) and exists in specific tissues, including the epidermis and small intestin...
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.1700138114
更新日期:2017-03-28 00:00:00
abstract::When long polymers such as DNA are in a highly concentrated state they may become entangled, leading to restricted self-diffusion. Here, we investigate the effect of molecular topology on diffusion in concentrated DNA solutions and find surprisingly large effects, even with molecules of modest length and concentration...
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.0700137104
更新日期:2007-03-20 00:00:00
abstract::New approaches to the study of early hominin diets have refreshed interest in how and when our diets diverged from those of other African apes. A trend toward significant consumption of C4 foods in hominins after this divergence has emerged as a landmark event in human evolution, with direct evidence provided by stabl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.2006221117
更新日期:2020-09-08 00:00:00
abstract::Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C ε (PKCε), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high-fat diet produces hepatic insulin resistance t...
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.1804379115
更新日期:2018-09-18 00:00:00
abstract::In a genetic screen of available T-DNA-mutagenized Arabidopsis populations for loci potentially involved in phytochrome (phy) signaling, we identified a mutant that displayed reduced seedling deetiolation under continuous red light, but little if any change in responsiveness to continuous far-red light. This behavior ...
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.170283997
更新日期:2000-08-15 00:00:00
abstract::Voltage-dependent anion channels (VDACs) are pore-forming proteins (porins) that form the major pathway for movement of adenine nucleotides through the outer mitochondrial membrane. Electrophysiological studies indicate that VDAC-like channel activity is also prevalent in the cell membranes of many mammalian cells. Ho...
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.060242297
更新日期:2000-03-28 00:00:00
abstract::Many neurotransmitters are known to regulate neuronal cell function by means of activation of cAMP-dependent protein kinase (PKA) and phosphorylation of neuronal substrate proteins, including transcription factors and ion channels. Here, we have characterized the gene expression of two isoforms of a protein kinase inh...
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.92.5.1734
更新日期:1995-02-28 00:00:00
abstract::We present a mechanism by which organisms with only a single photoreceptor, which have a monochromatic view of the world, can achieve color discrimination. An off-axis pupil and the principle of chromatic aberration (where different wavelengths come to focus at different distances behind a lens) can combine to provide...
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.1524578113
更新日期:2016-07-19 00:00:00
abstract::Small RNAs (sRNAs) are important components of posttranscriptional regulation. These molecules are prevalent in bacterial and eukaryotic organisms, and involved in a variety of responses to environmental stresses. The functional characterization of sRNAs is challenging and requires highly focused and extensive experim...
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.1104318108
更新日期:2011-09-13 00:00:00
abstract::Before they even speak, infants become attuned to the sounds of the language(s) they hear, processing native phonetic contrasts more easily than nonnative ones. For example, between 6 to 8 mo and 10 to 12 mo, infants learning American English get better at distinguishing English and [l], as in "rock" vs. "lock," relat...
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.2001844118
更新日期:2021-02-09 00:00:00
abstract::Measurements of the effect of DNA on rates of bimolecular energy transfer between ions provide a direct indication of how cations cluster in regions near DNA and how anions are repelled from the same regions. Energy transfer from luminescent lanthanide ions (in the "rapid-diffusion" limit) probes collision frequencies...
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.83.10.3267
更新日期:1986-05-01 00:00:00
abstract::We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It i...
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.2008013117
更新日期:2020-10-06 00:00:00
abstract::Rat liver glutamine synthetase (s(20,w) 15.0 S; MW about 352,000) resembles ovine brain glutamine synthetase in that it (a) has 8 subunits, (b) acts on both L- and D-glutamate and certain glutamate analogs (e.g., beta-glutamate, cis-cycloglutamate, and alpha-methyl-L-glutamate), and (c) is irreversibly inhibited by L-...
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.68.4.781
更新日期:1971-04-01 00:00:00
abstract::Wild-type newborn mice are characterized by the ability of certain liver-specific genes encoding various enzymes and mapping on different chromosomes to respond to glucocorticoid induction. Newborn mice homozygous for deletions at and around the albino locus on chromosome 7 fail to develop this competence for hormone-...
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.88.13.5607
更新日期:1991-07-01 00:00:00
abstract::The basidiomycete Ustilago maydis is the causative agent of the disease corn smut. To be pathogenic, strains of U. maydis must be heterozygous for a locus called "b," which appears to control both pathogenicity and sexual development. Two alleles of the b locus of U. maydis were isolated by complementation and hybridi...
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.86.3.978
更新日期:1989-02-01 00:00:00
abstract::Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calci...
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.0801027105
更新日期:2008-04-01 00:00:00
abstract::The proteasome is responsible for degradation of substrates of the ubiquitin pathway. 20S proteasomes are cylindrical particles with subunits arranged in a stack of four heptameric rings. The outer rings are composed of alpha subunits, and the inner rings are composed of beta subunits. A well-characterized archaeal 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.94.14.7156
更新日期:1997-07-08 00:00:00
abstract::Profilin2 (PFN2) is a target of the embryonic stem cell (ESC)-enriched miR-290 family of microRNAs (miRNAs) and an actin/dynamin-binding protein implicated in endocytosis. Here we show that the miR-290-PFN2 pathway regulates many aspects of ESC biology. In the absence of miRNAs, PFN2 is up-regulated in ESCs, with a re...
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.2002750117
更新日期:2020-08-25 00:00:00
abstract::The gene encoding the glycolytic enzyme triose-phosphate isomerase (TPI; EC 5.3.1.1) has been central to the long-standing controversy on the origin and evolutionary significance of spliceosomal introns by virtue of its pivotal support for the introns-early view, or exon theory of genes. Putative correlations between ...
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.92.18.8507
更新日期:1995-08-29 00:00:00
abstract::Cell fate determination depends in part on the establishment of specific transcriptional programs of gene expression. These programs result from the interpretation of the genomic cis-regulatory information by sequence-specific factors. Decoding this information in sequenced genomes is an important issue. Here, we deve...
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.1002876107
更新日期:2010-08-17 00:00:00
abstract::Glucocorticoids rapidly and completely inhibit intracellular plasminogen activator activity in rat hepatoma cells, as assayed by the solubilization of 125I-labeled fibrin. Experiments in which extracts of dexamethasone-treated cells are mixed with extracts of control cells demonstrate an inhibitor of protease activity...
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.75.12.6130
更新日期:1978-12-01 00:00:00
abstract::Maintenance of genome stability is essential for the accurate propagation of genetic information and cell growth and survival. Organisms have therefore developed efficient strategies to prevent DNA lesions and rearrangements. Much of the information concerning these strategies has been obtained through the study of ba...
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.0901710106
更新日期:2009-08-25 00:00:00
abstract::Four major neutralizing regions of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein were identified and characterized with a panel of 80 HIV-1 antibody-positive human sera. Levels of neutralizing antibodies against the HIV-1 strains IIIB, SF2, and RF were compared with reactivity in ELISAs against...
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.89.2.461
更新日期:1992-01-15 00:00:00
abstract::Coacervation is a common phenomenon in natural polymers and has been applied to synthetic materials systems for coatings, adhesives, and encapsulants. Single-component coacervates are formed when block polyampholytes exhibit self-coacervation, phase separating into a dense liquid coacervate phase rich in the polyampho...
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.1900435116
更新日期:2019-04-23 00:00:00
abstract::The charge density distribution of a protein has been refined experimentally. Diffraction data for a crambin crystal were measured to ultra-high resolution (0.54 A) at low temperature by using short-wavelength synchrotron radiation. The crystal structure was refined with a model for charged, nonspherical, multipolar a...
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.97.7.3171
更新日期:2000-03-28 00:00:00
abstract::During response of budding yeast to peptide mating pheromone, the cell becomes markedly polarized and MAPK scaffold protein Ste5 localizes to the resulting projection (shmoo tip). We demonstrated before that this recruitment is essential for sustained MAPK signaling and requires interaction of a pleckstrin homology (P...
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.1005817107
更新日期:2010-06-29 00:00:00
abstract::To clone the gene for the human Na+/H+ antiporter, we first constructed a stable mouse LTK- cell line (LAP1) lacking Na+/H+ antiport activity. Second, we devised a selective technique based on acid killing that specifically sorts out cells expressing low levels of Na+/H+ antiport activity from a population of antiport...
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.83.24.9388
更新日期:1986-12-01 00:00:00
abstract::Some of the most important impacts of global climate change will be felt among the populations, predominantly in developing countries, referred to as "subsistence" or "smallholder" farmers. Their vulnerability to climate change comes both from being predominantly located in the tropics, and from various socioeconomic,...
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.0701855104
更新日期:2007-12-11 00:00:00
abstract::Over the last decade a variety of MS measurements, such as HD exchange, collision cross sections, and electron capture dissociation (ECD), have been used to characterize protein folding in the gas phase, in the absence of solvent. To the extensive data already available on ubiquitin, here photofragmentation of its ECD...
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.212643599
更新日期:2002-12-10 00:00:00