Abstract:
:In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5 vaccine. We propose that this was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy volunteers. Dendritic cells (DCs) from these individuals were pulsed with replication defective Ad5 or Ad11 and co-cultured with autologous lymphocytes. Cytokine profiles, proliferative capacity, mucosal migration potential, and susceptibility to HIV infection of the adenovirus-stimulated memory CD4 T cells were measured. Stimulation of T cells from healthy Ad5-seropositive but Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors induced preferential expansion of adenovirus memory CD4 T cells expressing alpha(4)beta(7) integrins and CCR9, indicating a mucosal-homing phenotype. CD4 T-cell proliferation and IFN-gamma production in response to Ad stimulation correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher susceptibility to infection by R5 tropic HIV-1. This suggests that adenoviral-based vaccination against HIV-1 in individuals with preexisting immunity against Ad5 results in preferential expansion of HIV-susceptible activated CD4 T cells that home to mucosal tissues, increases the number of virus targets, and leads to a higher susceptibility to HIV acquisition.
journal_name
Proc Natl Acad Sci U S Aauthors
Benlahrech A,Harris J,Meiser A,Papagatsias T,Hornig J,Hayes P,Lieber A,Athanasopoulos T,Bachy V,Csomor E,Daniels R,Fisher K,Gotch F,Seymour L,Logan K,Barbagallo R,Klavinskis L,Dickson G,Patterson Sdoi
10.1073/pnas.0907898106subject
Has Abstractpub_date
2009-11-24 00:00:00pages
19940-5issue
47eissn
0027-8424issn
1091-6490pii
0907898106journal_volume
106pub_type
杂志文章abstract::Ig class-switch recombination (CSR) is a region-specific process that exchanges the constant Ig heavy-chain region and thus modifies an antibody's effector function. DNA lesions in switch (S) regions are induced by activation-induced cytidine deaminase (AID) and uracil-DNA glycosylase 2 (UNG2), subsequently processed ...
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.1012591108
更新日期:2010-12-21 00:00:00
abstract::The phosphatidylinositol 3-kinase subunit PIK3CA is frequently mutated in human cancers. Here we used gene targeting to "knock in" PIK3CA mutations into human breast epithelial cells to identify new therapeutic targets associated with oncogenic PIK3CA. Mutant PIK3CA knockin cells were capable of epidermal growth facto...
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.0813351106
更新日期:2009-02-24 00:00:00
abstract::The unprecedented scale of the Ebola outbreak in Western Africa (2014-2015) has prompted an explosion of efforts to understand the transmission dynamics of the virus and to analyze the performance of possible containment strategies. Models have focused primarily on the reproductive numbers of the disease that represen...
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.1614595114
更新日期:2017-02-28 00:00:00
abstract::Evolution of an oxygenic atmosphere required primordial life to accommodate the toxicity associated with reactive oxygen species. We have characterized an archaeal antioxidant from the hyperthermophilic acidophile Sulfolobus solfataricus. The amino acid sequence of this approximately 22-kDa protein shares little 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.0501497102
更新日期:2005-07-26 00:00:00
abstract::Protein S (ProS) and growth arrest-specific 6 (Gas6) bind to phosphatidylserine (PtdSer) and induce efferocytosis upon binding TAM-family receptors (Tyro3, Axl, and Mer). Here, we produced mouse ProS, Gas6, and TAM-receptor extracellular region fused to IgG fragment crystallizable region in HEK293T cells. ProS and Gas...
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.1705365114
更新日期:2017-08-15 00:00:00
abstract::A metabolic mechanism for oxalic acid biosynthesis in the wood-rotting basidiomycete Fomitopsis palustris has been proposed on the basis of biochemical analyses of glucose metabolism. There was a strong correlation between glucose consumption and oxalate production. Oxalic acid was found to accumulate in the culture 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.191389598
更新日期:2001-09-25 00:00:00
abstract::Mutational processes of simple sequence repeats (SSRs) in complex genomes are poorly understood. We examined these processes by introducing a two-phase mutation model. In this model, most mutations are single-step changes, but infrequent large jumps in repeat number also occur. We used computer simulations to determin...
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.91.8.3166
更新日期:1994-04-12 00:00:00
abstract::Grain growth under shear annealing is crucial for controlling the properties of polycrystalline materials. However, their microscopic kinetics are not well understood because individual atomic trajectories are difficult to track. Here, we study grain growth with single-particle kinetics in colloidal polycrystals using...
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.2013456117
更新日期:2020-09-29 00:00:00
abstract::Artemisinins are effective against a variety of parasites and provide the first line of treatment for malaria. Laboratory studies have identified several mechanisms for artemisinin resistance in Plasmodium falciparum, including mutations in Kelch13 that are associated with delayed clearance in some clinical isolates, ...
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.1914732116
更新日期:2019-12-05 00:00:00
abstract::The past two decades have seen an enormous growth in the field of human brain mapping. Investigators have extensively exploited techniques such as positron emission tomography and MRI to map patterns of brain activity based on changes in cerebral hemodynamics. However, until recently, most studies have investigated eq...
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.95.3.773
更新日期:1998-02-03 00:00:00
abstract::Predicting whether and how populations will adapt to rapid climate change is a critical goal for evolutionary biology. To examine the genetic basis of fitness and predict adaptive evolution in novel climates with seasonal variation, we grew a diverse panel of the annual plant Arabidopsis thaliana (multiparent advanced...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 评论,杂志文章
doi:10.1073/pnas.1517456113
更新日期:2016-05-17 00:00:00
abstract::A large number of primary petite (rho-) clones were isolated after ethidium bromide mutagenesis of various grande (rho+) strains of S. cerevisiae that contained the mitochondrial genetic markers, CR, ER, OIR (or OIIR), and PR. From the frequency of coretention of markers in the petites, we have deduced a probable circ...
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.73.12.4608
更新日期:1976-12-01 00:00:00
abstract::Na(+)-channel inactivation is proposed to occur by binding of an intracellular inactivation gate to a hydrophobic inactivation gate receptor in the intracellular mouth of the pore. Amino acid residues in transmembrane segment S6 of domain IV (IVS6) that are critical for fast inactivation were identified by alanine-sca...
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.91.25.12346
更新日期:1994-12-06 00:00:00
abstract::The functional architecture of mammalian visual cortex has been elucidated in impressive detail by experimental work of the past 20-25 years. The origin of many of the salient features of this architecture, however, has remained unexplained. This paper is the first of three (the others will appear in subsequent issues...
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.83.19.7508
更新日期:1986-10-01 00:00:00
abstract::Low-frequency thalamocortical oscillations that underlie drowsiness and slow-wave sleep depend on rhythmic inhibition of relay cells by neurons in the reticular nucleus (RTN) under the influence of corticothalamic fibers that branch to innervate RTN neurons and relay neurons. To generate oscillations, input to RTN pre...
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.061013698
更新日期:2001-03-27 00:00:00
abstract::The endometrial epithelium of the uterus regenerates periodically. The cellular source of newly regenerated endometrial epithelia during a mouse estrous cycle or a human menstrual cycle is presently unknown. Here, I have used single-cell lineage tracing in the whole mouse uterus to demonstrate that epithelial stem cel...
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.1814597116
更新日期:2019-04-02 00:00:00
abstract::Two regions of human thyrotropin (thyroid-stimulating hormone, TSH) receptor (TSHR) (residues 12-44 and 308-364) were selected on the basis that they exhibit no sequence resemblance to luteinizing hormone/chorionic gonadotropin receptor. Five synthetic overlapping peptides (12-30, 24-44, 308-328, 324-344, and 339-364)...
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.88.9.3613
更新日期:1991-05-01 00:00:00
abstract::Rodless retina (gene symbol, r) was discovered in mice by Keeler 70 years ago and was first described in this journal as an autosomal recessive mutation leading to "the absence of the visual cells (rods), the external nuclear layer, and the external molecular layer" [Keeler, C. E. (1924) Proc. Natl. Acad. Sci. USA 10,...
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.90.20.9616
更新日期:1993-10-15 00:00:00
abstract::Okadaic acid is a non-phorbol 12-myristate 13-acetate (PMA)-type tumor promoter on mouse skin and known to be a potent inhibitor of serine/threonine protein phosphatases. Contrary to expectation from its tumor-promoting activity, okadaic acid was shown to have a potential to revert the phenotypes of cells transformed ...
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.86.24.9946
更新日期:1989-12-01 00:00:00
abstract::Maintaining the fidelity of nascent peptide chain (NP) synthesis is essential for proteome integrity and cellular health. Ribosome-associated quality control (RQC) serves to resolve stalled translation, during which untemplated Ala/Thr residues are added C terminally to stalled peptide, as shown during C-terminal Ala ...
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.2005506117
更新日期:2020-10-06 00:00:00
abstract::The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral...
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.90.8.3127
更新日期:1993-04-15 00:00:00
abstract::Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4(+) T cells. Such in...
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.1302634110
更新日期:2013-07-16 00:00:00
abstract::Intrinsically disordered proteins (IDPs) are involved in a wide range of regulatory processes in the cell. Owing to their flexibility, their conformations are expected to be particularly sensitive to the crowded cellular environment. Here we use single-molecule Förster resonance energy transfer to quantify the effect ...
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.1322611111
更新日期:2014-04-01 00:00:00
abstract::Systemic inflammation occurring around the course of tumor progression and treatment are often correlated with adverse oncological outcomes. As such, it is suspected that neutrophils, the first line of defense against infection, may play important roles in linking inflammation and metastatic seeding. To decipher the 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.1715932115
更新日期:2018-07-03 00:00:00
abstract::The exocytosis of AMPA receptors is a key step in long-term potentiation (LTP), yet the timing and location of exocytosis and the signaling pathways involved in exocytosis during synaptic plasticity are not fully understood. Here we combine two-photon uncaging with two-photon imaging of a fluorescent label of surface ...
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.0913875107
更新日期:2010-09-07 00:00:00
abstract::cDNAs made from polyadenylylated RNAs of the mouse lens were cloned by the G.C tailing procedure in the bacterial plasmid pBR322. Four recombinant DNAs containing gamma-crystallin sequences were identified by hybrid selection and translation. Sequence analysis of the in vivo-labeled gamma-crystallin polypeptides that ...
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.79.9.2783
更新日期:1982-05-01 00:00:00
abstract::The cingulate gyri in 37 subjects with and without early dementia of the Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution. Groups were segregated into young controls (n = 10), age-matched normal controls (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated Bayesian se...
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.2136624100
更新日期:2003-12-09 00:00:00
abstract::In eukaryotic cells, RAD52 protein plays a central role in genetic recombination and DNA repair by (i) promoting the annealing of complementary single-stranded DNA and (ii) stimulation of the RAD51 recombinase. The single-strand annealing domain resides in the N-terminal region of the protein and is highly conserved, ...
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.212449899
更新日期:2002-10-15 00:00:00
abstract::A major calmodulin-binding protein (CaM-BP) of Mr 240,000 was demonstrated in various rat tissues by using a 125I-labeled CaM gel overlay technique. This protein (designated p240) was detected in the particulate fraction and to a lesser extent in the cytosol of all tissues studied. Binding of CaM to p240 was completel...
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.79.12.3780
更新日期:1982-06-01 00:00:00
abstract::In contrast to the immunosuppressive potential of UVB (280-320 nm) radiation in experimental animals and humans, UVA (320-400 nm) radiation at environmentally relevant doses appears to be immunologically inert. However, such exposure to UVA radiation has been observed unexpectedly to induce resistance to UVB-induced 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.96.16.9317
更新日期:1999-08-03 00:00:00