Abstract:
:Neonates suffer high morbidity and mortality in infection, presumably because of the lack of a fully developed adaptive and innate immune system. Evidence of poor innate responses in neonates has been shown by using a model that sensitizes the host to Toll-like receptor (TLR)-mediated inflammation with d-galactosamine (d-GalN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LPS stimulation, and such hypersensitivity extends to other TLR agonists including actual viral infection. Our study reveals that the ensuing inflammatory reaction after d-GalN sensitization reflects preferential toxicity of d-GalN to adult liver cells, rather than accurately reflecting the TLR response to LPS. We show further that an uncontrolled proinflammatory innate response due to inadequate T cells makes neonates more vulnerable to TLR agonists or viral infection. Remarkably, through transfer of T cells into neonates or depletion of T cells in adult mice, we show that T cells are sufficient and necessary to control the early inflammatory response to LPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhao J,Kim KD,Yang X,Auh S,Fu YX,Tang Hdoi
10.1073/pnas.0800152105subject
Has Abstractpub_date
2008-05-27 00:00:00pages
7528-33issue
21eissn
0027-8424issn
1091-6490pii
0800152105journal_volume
105pub_type
杂志文章abstract::Lactate racemase is the first enzyme known to possess a metal pincer active site. The enzyme interconverts d- and l-lactic acid, which is important for the assembly of cell walls in many microorganisms. Here, we report a synthetic model of the active site of lactate racemase, which features a pyridinium-based SCS pinc...
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.1616038114
更新日期:2017-02-07 00:00:00
abstract::The lac operon of Escherichia coli spans approximately 5300 base pairs and includes the lacZ, lacY, and lacA genes in addition to the operator, promoter, and transcription termination regions. We report here the sequence of the lacA gene and the region distal to it, confirming the sequence of thiogalactoside transacet...
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.82.19.6414
更新日期:1985-10-01 00:00:00
abstract::The first step in the replication of the adenovirus genome is the covalent attachment of the 5'-terminal nucleotide, dCMP, to the virus-encoded terminal protein precursor (pTP). This reaction can be observed in vitro and has been previously shown to be dependent upon either viral DNA or linearized plasmid DNA containi...
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.81.1.100
更新日期:1984-01-01 00:00:00
abstract::The approximately 30-kb coronavirus (+)RNA genome is replicated and transcribed by a membrane-bound replicase complex made up of 16 viral nonstructural proteins (nsp) with multiple enzymatic activities. The complex includes an RNA endonuclease, NendoU, that is conserved among nidoviruses but no other RNA virus, making...
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.0601708103
更新日期:2006-08-08 00:00:00
abstract::When propagated on arl strains (a subclass of Escherichia coli hyper-rec mutants), lambda "Red-" duplication phages accumulated an enhanced potential for recombination. The physical properties of the recombinogenic phages thus obtained ("Arl-" phages) were similar to those of phages grown on arl+ bacteria. However, Ar...
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.76.12.6066
更新日期:1979-12-01 00:00:00
abstract::The absorption spectrum of an activesite specific chromophoric acyl enzyme, sturgeon beta-(2-furyl)-acryloyl-glyceraldehyde-3-phosphate dehydrogenase, is reported. This acyl enzyme undergoes all of the catalyzed reactions characteristic of the intermediate of the physiological acyl enzyme, 3-phospho-D-glyceroyl-glycer...
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.70.7.2077
更新日期:1973-07-01 00:00:00
abstract::Theoretical and experimental optical, redox, and paramagnetic results are presented for models of siroheme, the iron isobacteriochlorin prosthetic group of nitrite and sulfite reductases, and of sirohydrochlorin, the metal-free siroheme that is an intermediate in the biosynthetic pathway to vitamin B(12). The facile 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.78.5.2652
更新日期:1981-05-01 00:00:00
abstract::Erythropoietin regulates the proliferation and differentiation of erythroid precursor cells. Its effect is mediated by the erythropoietin receptor (EPOR), a member of a large family of cytokine receptors. The EPOR gene has recently been cloned, sequenced, and characterized. As shown experimentally, its intracellular 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.90.10.4495
更新日期:1993-05-15 00:00:00
abstract::Total nuclear proteins extracted from cell lines representing various stages of differentiation of mouse B lymphocytes were studied by computer analysis of two-dimensional gels. Of the 1438 spots present on the gels, 55 varied significantly in intensity during differentiation. The variations occurred most often in ste...
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.88.5.1830
更新日期:1991-03-01 00:00:00
abstract::Major changes in global rainfall patterns accompanied a northward shift of Earth's thermal equator at the onset of an abrupt climate change 14.6 kya. This northward pull of Earth's wind and rain belts stemmed from disintegration of North Atlantic winter sea ice cover, which steepened the interhemispheric meridional te...
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.1301855110
更新日期:2013-10-15 00:00:00
abstract::Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK functi...
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.1614894114
更新日期:2017-04-11 00:00:00
abstract::Hypercholesterolemia, high serum cholesterol in the form of LDL, is a major risk factor for atherosclerosis. LDL is mostly degraded in the liver after its cellular internalization with the LDL receptor (LDLR). This clathrin-mediated endocytosis depends on the protein autosomal recessive hypercholesterolemia (ARH), whi...
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.1114128109
更新日期:2012-05-01 00:00:00
abstract::Despite their relative simplicity, bacteria have complex anatomy at the subcellular level. At the cell poles of Caulobacter crescentus, a 177-amino acid (aa) protein called PopZ self-assembles into 3D polymeric superstructures. Remarkably, we find that this assemblage interacts directly with at least eight different 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.1602380113
更新日期:2016-11-01 00:00:00
abstract::Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outco...
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.1912546116
更新日期:2020-01-07 00:00:00
abstract::Aptamers recognize their targets with extraordinary affinity and specificity. The aptamer-based therapeutic, Macugen, is derived from a modified 2'fluoro pyrimidine RNA inhibitor to vascular endothelial growth factor (VEGF) and is now being used to treat the wet form of age-related macular degeneration. This VEGF(165)...
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.0509069102
更新日期:2005-12-27 00:00:00
abstract::Under anesthesia with sodium pentobarbital, the sciatic nerves of rats were transected bilaterally, and a catheter was inserted into the central end of the left renal artery. After an initial flush, an Alzet pump was attached to the catheter, containing various concentrations of glycyl-L-glutamine (Gly-Gln), methylpre...
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.87.23.9495
更新日期:1990-12-01 00:00:00
abstract::Introduction of a sequence encoding 147 amino acids from human immunodeficiency virus type I (HIV-1) strain MN glycoprotein gp120 into the RNA genome of the stably attenuated Mengo virus strain vM16 yielded an infectious recombinant virus, vMLN450, which expressed the heterologous HIV-1 sequence along with the normal ...
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.91.21.9775
更新日期:1994-10-11 00:00:00
abstract::Recent functional imaging studies have revealed coactivation in a distributed network of cortical regions that characterizes the resting state, or default mode, of the human brain. Among the brain regions implicated in this network, several, including the posterior cingulate cortex and inferior parietal lobes, have al...
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.0308627101
更新日期:2004-03-30 00:00:00
abstract::The phosphatase and tensin homolog (PTEN) is a tumor suppressor that is inactivated in many human cancers. PTEN loss has been associated with resistance to inhibitors of the epidermal growth factor receptor (EGFR), but the molecular basis of this resistance is unclear. It is believed that unopposed phosphatidylinosito...
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.0911188107
更新日期:2010-04-06 00:00:00
abstract::A pH-dependent transition between delocalized and trapped mixed valence states of an engineered CuA center in azurin has been investigated by UV-visible absorption and electron paramagnetic resonance spectroscopic techniques. At pH 7.0, the CuA azurin displays a typical delocalized mixed valence dinuclear [Cu(1.5).......
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.0403473101
更新日期:2004-08-31 00:00:00
abstract::Adjacent paraffin sections of rat hypothalami fixed in Bouin's fluid were treated either with buffer or with luteinizing hormone-releasing hormone (LHRH) before immunocytochemical staining with anti-LHRH. Upon buffer pretreatment, pituitary gonadotrophs were unstained and hypothalamic fibers were stained. Upon LHRH 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.78.8.5216
更新日期:1981-08-01 00:00:00
abstract::The plasma concentration of the major vitamin D metabolites; 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D were measured during pregnancy and lactation in the adult female rat. The concentrations of these metabolites were also measured in rat pups during lactation and after weaning. The pl...
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.76.11.5549
更新日期:1979-11-01 00:00:00
abstract::The role of geographic isolation in marine microbial speciation is hotly debated because of the high dispersal potential and large population sizes of planktonic microorganisms and the apparent lack of strong dispersal barriers in the open sea. Here, we show that gene flow between distant populations of the globally d...
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.1001380107
更新日期:2010-07-20 00:00:00
abstract::Endosomal cargo travels through a dynamic vesicle network en route to degradation by lysosomes or recycling through the Golgi apparatus back to the cell surface. Rab5 is a key determinant of the early endosomes by organizing effector proteins in specific subdomains and mediating early endosome fusion. We find that ear...
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.0711707105
更新日期:2008-06-10 00:00:00
abstract::To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the ma...
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.86.23.9456
更新日期:1989-12-01 00:00:00
abstract::Molecular imaging probes have potential for in vivo identification of apoptosis and other intracellular processes. TcapQ, a cell-penetrating, near-infrared fluorescent peptide probe designed to be optically silent through intramolecular fluorescence quenching and activated by effector caspases, has been previously des...
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.0812884106
更新日期:2009-06-09 00:00:00
abstract::The structure of promoter chromatin determines the ability of transcription factors (TFs) to bind to DNA and therefore has a profound effect on the expression levels of genes. However, the role of spontaneous nucleosome movements in this process is not fully understood. Here, we developed a single-molecule optical twe...
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.1815424116
更新日期:2019-06-18 00:00:00
abstract::A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance--wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on f...
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.1423952112
更新日期:2015-01-27 00:00:00
abstract::The mode of action of "allogeneic supernatant" (the culture supernatant of a 24-hr mixedlymphocyte reaction), has been studied. This factor stimulates the response of spleen cell cultures depleted in thymus-derived lymphoid cells (T-cells) to antigens that elicit a thymus-dependent response. We used a limiting dilutio...
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.71.2.512
更新日期:1974-02-01 00:00:00
abstract::We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes bo...
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.95.18.10774
更新日期:1998-09-01 00:00:00