Abstract:
:To understand the role of the immune system in limiting HIV type 1 replication, it is critical to know to what extent the rapid turnover of productively infected cells is caused by viral cytopathicity or by immune-mediated lysis. We show that uncultured peripheral blood mononuclear cells of many patients contain cytotoxic T lymphocytes (CTL) that lyse target cells-at plausible peripheral blood mononuclear cell-to-target ratios-with half-lives of less than 1 day. In 23 patients with CD4 counts ranging from 10 to 900 per microliter, the average rate of CTL-mediated lysis corresponds to a target cell half-life of 0.7 day. We develop mathematical models to calculate the turnover rate of infected cells subjected to immune-mediated lysis and viral cytopathicity and to estimate the fraction of cells that are killed by CTL as opposed to virus. The models provide new interpretations of drug treatment dynamics and explain why the observed rate of virus decline is roughly constant for different patients. We conclude that in HIV type 1 infection, CTL-mediated lysis can reduce virus load by limiting virus production, with small effects on the half-life of infected cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Klenerman P,Phillips RE,Rinaldo CR,Wahl LM,Ogg G,May RM,McMichael AJ,Nowak MAdoi
10.1073/pnas.93.26.15323subject
Has Abstractpub_date
1996-12-24 00:00:00pages
15323-8issue
26eissn
0027-8424issn
1091-6490journal_volume
93pub_type
杂志文章abstract::The traditional morphologically grounded placement of South American guinea pig-like rodents (Caviomorpha) within one of the two rodent suborders, Hystricognathi, has been disputed by recent analysis of protein and nucleic acid sequence data. The Caviomorpha and possibly all Hystricognathi would be considered a separa...
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.90.20.9698
更新日期:1993-10-15 00:00:00
abstract::The earliest folding events in single-tryptophan mutants of RNase A were investigated by fluorescence measurements by using a combination of stopped-flow and continuous-flow mixing experiments covering the time range from 70 micros to 10 s. An ultrarapid double-jump mixing protocol was used to study refolding from an ...
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.0407999101
更新日期:2004-12-21 00:00:00
abstract::When deprived of D-glucose for 24 hr, chicken embryo fibroblasts exhibit a marked increase in hexose transport activity compared with that of control cells. Scatchard analysis of [3H]cytochalasin B binding to starved cell plasma membranes (46 pmol/mg) indicated a six-fold increase compared with fed cell plasma membran...
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.79.7.2286
更新日期:1982-04-01 00:00:00
abstract::Neutrophils and dendritic cells when migrating in confined environments have been shown to actuate a directional choice toward paths of least hydraulic resistance (barotaxis), in some cases overriding chemotactic responses. Here, we investigate whether this barotactic response is conserved in the more primitive model ...
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.2000686117
更新日期:2020-10-13 00:00:00
abstract::Protein misfolding is the molecular basis for several human diseases. How the primary amino acid sequence triggers misfolding and determines the benign or toxic character of the misfolded protein remains largely obscure. Among proteins that misfold, polyglutamine (polyQ) expansion proteins provide an interesting case:...
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.0604547103
更新日期:2006-07-18 00:00:00
abstract::The unicellular green alga Chlamydomonas swims with two flagella that can synchronize their beat. Synchronized beating is required to swim both fast and straight. A long-standing hypothesis proposes that synchronization of flagella results from hydrodynamic coupling, but the details are not understood. Here, we presen...
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.1300895110
更新日期:2013-11-05 00:00:00
abstract::A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 r...
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.89.23.11579
更新日期:1992-12-01 00:00:00
abstract::Bacteriophage T3-induced RNA polymerase, upon copying its specific template, native T3 DNA, initiates RNA chains only with GTP. Denaturation of the DNA results in loss of template specificity for the polymerase. With denatured T3 DNA as template, T3 polymerase initiates RNA chains with both ATP and GTP, and the averag...
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.69.1.55
更新日期:1972-01-01 00:00:00
abstract::FUS3 is functionally redundant with KSS1, a homologous yeast protein kinase, for a step(s) in signal transduction between the beta subunit of the guanine nucleotide binding protein (G protein), STE4, and the mating type-specific transcriptional activator, STE12. Either FUS3 or KSS1 can execute this function; when neit...
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.88.21.9392
更新日期:1991-11-01 00:00:00
abstract::We have developed a high-throughput approach to the labor-intensive problems of DNA cyclization, which we use to characterize DNA curvature and mechanical properties. The method includes a combinatorial approach to make the DNA constructs needed and automated real-time measurement of the kinetics using fluorescence. W...
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.0530189100
更新日期:2003-03-18 00:00:00
abstract::Isolated human erythrocyte spectrin is a dimer of two unique polypeptide chains. The dimer (alpha beta) undergoes reversible salt- and temperature-dependent association to form (alpha beta)2 tetramers. Spectrin also binds with high affinity to a protein receptor on the cytoplasmic surface of erythrocyte membrane vesic...
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.77.11.6592
更新日期:1980-11-01 00:00:00
abstract::An oligomeric intermediate in the biosynthetic pathway of peptidoglycan was isolated from B. megaterium. The oligomer has been identified as [disaccharide(pentapeptide)]12 pyrophosphoryl undecaprenol. ...
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.73.11.4200
更新日期:1976-11-01 00:00:00
abstract::A murine hybridoma-derived antibody (IPH.134) has been produced which has apparent high binding specificity for an extract of Schistosoma japonicum adult worms. No binding was detected to extracts of S. japonicum eggs or to extracts from other adult trematodes (Fasciola hepatica, Paragonimus westermanii, Clonorchis 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.78.5.3165
更新日期:1981-05-01 00:00:00
abstract::The conservation of developmental functions exerted by Antp-class homeoproteins in protostomes and deuterostomes suggested that homologs with related functions are present in diploblastic animals. Our phylogenetic analyses showed that Antp-class homeodomains belong either to non-Hox or to Hox/paraHox families. Among 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.97.9.4493
更新日期:2000-04-25 00:00:00
abstract::The role of microtubules in 3H-labeled protein secretion in rat lacrimal glands was probed by the use of colchicine and two of its analogues that reversibly bind to tubulin. These analogues were 2-methoxy-5-(2,3,4,4'-trimethoxyphenyl)-2,4,6-cycloheptatriene-1-o ne and 2,3,4,4'-tetramethoxy-1,1'-biphenyl, the latter ha...
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.86.12.4515
更新日期:1989-06-01 00:00:00
abstract::Translocations involving chromosome band 11q23, found in acute lymphoid and myeloid leukemias, disrupt the MLL gene. This gene encodes a putative transcription factor with homology to the zinc fingers and other domains of the Drosophila trithorax gene product and to the "AT-hook" motif of high mobility group proteins....
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.91.22.10610
更新日期:1994-10-25 00:00:00
abstract::All science has uncertainty. Unless that uncertainty is communicated effectively, decision makers may put too much or too little faith in it. The information that needs to be communicated depends on the decisions that people face. Are they (i) looking for a signal (e.g., whether to evacuate before a hurricane), (ii) 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.1317504111
更新日期:2014-09-16 00:00:00
abstract::Gene function is typically evaluated by sampling the continuum of gene expression at only a few discrete points corresponding to gene knockout or overexpression. We argue that this characterization is incomplete and present a library of engineered promoters of varying strengths obtained through mutagenesis of a consti...
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.0504604102
更新日期:2005-09-06 00:00:00
abstract::Leucine-rich repeat kinase 2 (LRRK2) has been associated with a variety of human diseases, including Parkinson's disease and Crohn's disease, whereas LRRK2 deficiency leads to accumulation of abnormal lysosomes in aged animals. However, the cellular roles and mechanisms of LRRK2-mediated lysosomal regulation have rema...
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.1812196115
更新日期:2018-09-25 00:00:00
abstract::Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness. We examined the role of TH metabolism during ventilator-induced lung injury (VILI) in mice. Mice exposed to VILI recapitulated the serum TH findings of acute illness, namely a decrease 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.1109926108
更新日期:2011-12-06 00:00:00
abstract::Despite its popularity, chromatin immunoprecipitation followed by sequencing (ChIP-seq) remains a tedious (>2 d), manually intensive, low-sensitivity and low-throughput approach. Here, we combine principles of microengineering, surface chemistry, and molecular biology to address the major limitations of standard ChIP-...
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.1913261117
更新日期:2020-06-16 00:00:00
abstract::The small-component origins of herpes simplex virus 1 DNA synthesis are transcribed late in infection by an RNA with heterogeneous initiation sites approximately 290-360 base pairs from the origins. We report that cellular proteins react with a labeled RNA probe representing the 5' terminus of a subset of this RNA but...
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.86.17.6518
更新日期:1989-09-01 00:00:00
abstract::Mutations at the mouse limb deformity (ld) locus result in defects of growth and patterning of the limb and kidney during embryonic development. The gene responsible for this phenotype is large and complex, with the capacity to generate a number of alternatively spliced messenger RNA transcripts encoding nuclear 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.90.12.5554
更新日期:1993-06-15 00:00:00
abstract::Visual development is thought to be completed at an early age. We suggest that the maturation of the visual brain is not homogeneous: functions with greater need for early availability, such as visuomotor control, mature earlier, and the development of other visual functions may extend well into childhood. We found 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.96.21.12204
更新日期:1999-10-12 00:00:00
abstract::We show that a large class of finite factors has free entropy dimension less than or equal to one. This class includes all prime factors and many property T factors. ...
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.97.18.9881
更新日期:2000-08-29 00:00:00
abstract::As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated inter-leukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. We now demonstrate that when cloned interle...
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.85.2.569
更新日期:1988-01-01 00:00:00
abstract::Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver...
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.1613392114
更新日期:2017-04-11 00:00:00
abstract::Circadian rhythms modulate many aspects of physiology. Knowledge of the molecular basis of these rhythms has exploded in the last 20 years. However, most of these data are from model organisms, and translation to clinical practice has been limited. Here, we present an approach to identify molecular rhythms in humans 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.1619320114
更新日期:2017-05-16 00:00:00
abstract::Leukocytes normally marginate toward the vascular wall in large vessels and within the microvasculature. Reversal of this process, leukocyte demargination, leads to substantial increases in the clinical white blood cell and granulocyte count and is a well-documented effect of glucocorticoid and catecholamine hormones,...
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.1508920113
更新日期:2016-02-23 00:00:00
abstract::Different experimental structures of the same protein or of proteins with high sequence similarity contain many small variations. Here we construct ensembles of "high-sequence similarity Protein Data Bank" (HSP) structures and consider the extent to which such ensembles represent the structural heterogeneity of the na...
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.0511156103
更新日期:2006-07-18 00:00:00