Abstract:
:Human immunodeficiency virus type 1 (HIV-1) viral DNA synthesis in quiescent and activated peripheral blood lymphocytes (PBLs) was studied. Incomplete viral DNA (previously demonstrated to be associated with HIV-1 virions) is carried by HIV-1 virions into quiescent and activated PBLs, contributing to the formation of an early viral DNA pool in these cells. The viral DNA is subsequently completed but only extremely slowly and inefficiently in quiescent PBLs compared to that in stimulated PBLs. We find that this correlates with significantly lower levels of dNTP substrates in quiescent compared to activated PBLs. At these low dNTP concentrations, HIV-1 reverse transcriptase acts in a partially distributive manner. Increasing dNTP concentrations from the levels of quiescent PBLs to the levels of activated PBLs increases the processive action of reverse transcriptase, which in turn stimulates rapid and efficient formation of full-length DNA. Furthermore, hydroxyurea treatment of stimulated PBLs decreases the dNTP levels and the DNA synthesis rate to levels comparable to quiescent PBLs. Our data therefore indicate that low levels of dNTP may explain why HIV-1 DNA is synthesized slowly and inefficiently in quiescent PBLs and suggest that pharmacologic induction of low dNTP levels represents a therapeutic approach for inhibition of HIV-1 replication.
journal_name
Proc Natl Acad Sci U S Aauthors
Gao WY,Cara A,Gallo RC,Lori Fdoi
10.1073/pnas.90.19.8925subject
Has Abstractpub_date
1993-10-01 00:00:00pages
8925-8issue
19eissn
0027-8424issn
1091-6490journal_volume
90pub_type
杂志文章abstract::RNA movements and localization pervade biology, from embryonic development to disease. To identify RNAs at specific locations, we developed a strategy in which a uridine-adding enzyme is anchored to subcellular sites, where it directly marks RNAs with 3' terminal uridines. This localized RNA recording approach yields ...
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.1921408117
更新日期:2020-09-22 00:00:00
abstract::Two precursors to Chinook salmon (Oncorhynchus tshawytscha) melanin-concentrating hormone, an important factor in teleosts involved in the control of skin pigmentation and stress responsiveness, have been identified from DNA sequence analysis. Both precursors encode proteins of 132 amino acids and they share 107/132 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.86.11.4292
更新日期:1989-06-01 00:00:00
abstract::Fifteen tumor-containing specimens were obtained directly from patients with small cell carcinoma of the lung and tested for their ability to grow in serum-supplemented medium and in serum-free medium supplemented with hydrocortisone, insulin, transferrin, estrogen, and selenium (HITES). The tumor cells replicated 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.78.5.3185
更新日期:1981-05-01 00:00:00
abstract::A renin promoter-large tumor antigen (T antigen) fusion gene was constructed to provide a reporter function for renin expression in transgenic mice. These transgenic mice gave rise to tumors in subcutaneous soft tissue, which was attributed to transgene expression at this site. An immunohistochemical analysis of trans...
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.87.20.7993
更新日期:1990-10-01 00:00:00
abstract::Human capabilities in manipulating many different tools with dexterity suggest modular neural organization at functional levels, but anatomical modularity underlying the capabilities has yet to be demonstrated. Although modularity in phylogenetically older parts of the cerebellum is well known, comparable modularity 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.0835746100
更新日期:2003-04-29 00:00:00
abstract::Recent climate change has increased arctic soil temperatures and thawed large areas of permafrost, allowing for microbial respiration of previously frozen C. Furthermore, soil destabilization from melting ice has caused an increase in thermokarst failures that expose buried C and release dissolved organic C (DOC) to s...
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.1214104110
更新日期:2013-02-26 00:00:00
abstract::Single cortical neurons in the mammalian brain receive signals arising from multiple sensory input channels. Dendritic integration of these afferent signals is critical in determining the amplitude and time course of the neurons' output signals. As of yet, little is known about the spatial and temporal organization of...
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.1112355108
更新日期:2011-09-13 00:00:00
abstract::Transcriptional activation by steroid hormones is often associated with the appearance of a DNase I hypersensitive site resulting from a local alteration of the nucleoprotein structure of the promoter. For the mouse mammary tumor virus long terminal repeat, a viral promoter under glucocorticoid control, a model has be...
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.87.23.9300
更新日期:1990-12-01 00:00:00
abstract::The structure of cellulose microfibrils in wood is not known in detail, despite the abundance of cellulose in woody biomass and its importance for biology, energy, and engineering. The structure of the microfibrils of spruce wood cellulose was investigated using a range of spectroscopic methods coupled to small-angle ...
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.1108942108
更新日期:2011-11-22 00:00:00
abstract::Macrophage responses to Francisella infection have been characterized previously by subdued proinflammatory responses; however, these studies have generally focused on macrophage cell lines or monocyte-derived macrophages. Therefore, we studied the ability of fresh human blood monocytes to engulf and respond to Franci...
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.0504271103
更新日期:2006-01-03 00:00:00
abstract::Osteogenin was recently purified and the amino acid sequences of tryptic peptides were determined. Osteogenin in conjunction with insoluble collagenous bone matrix induces cartilage and bone formation in vivo. To understand the mechanism of action of osteogenin, we examined its influence on periosteal cells, osteoblas...
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.86.22.8793
更新日期:1989-11-01 00:00:00
abstract::Visual receptive fields (RFs) were mapped inside and outside the cortical representation of the optic disk in the striate cortex (area V1) of anesthetized and paralyzed Cebus monkeys. Unexpectedly, most cells were found to be binocularly driven, and the RFs mapped with contralateral-eye stimulation progressed in a top...
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.89.18.8547
更新日期:1992-09-15 00:00:00
abstract::Archaea of the phylum Thaumarchaeota are among the most abundant prokaryotes on Earth and are widely distributed in marine, terrestrial, and geothermal environments. All studied Thaumarchaeota couple the oxidation of ammonia at extremely low concentrations with carbon fixation. As the predominant nitrifiers in the oce...
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.1402028111
更新日期:2014-06-03 00:00:00
abstract::The crystal structure of the dimeric gene V protein of bacteriophage f1 was determined using multiwavelength anomalous diffraction on the selenomethionine-containing wild-type and isoleucine-47-->methionine mutant proteins with x-ray diffraction data phased to 2.5 A resolution. The structure of the wild-type protein h...
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.91.6.2071
更新日期:1994-03-15 00:00:00
abstract::T-cell migration into tissue depends on a cascade of rapid and selective adhesive interactions with endothelium. "Triggering" is a step in that cascade required to activate T-cell integrins. Hepatocyte growth factor (HGF) may be a physiologically relevant trigger, since we demonstrate that HGF can induce both adhesion...
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.91.15.7144
更新日期:1994-07-19 00:00:00
abstract::T cell-mediated autoimmune diseases such as type 1 diabetes (T1D) are believed to be the result in part of inefficient negative selection of self-specific thymocytes. However, the events regulating thymic negative selection are not fully understood. In the current study, we demonstrate that nonobese diabetic (NOD) mic...
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.0900683106
更新日期:2009-03-24 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::In the retina, dopamine plays a central role in neural adaptation to light. Progress in the study of dopaminergic amacrine (DA) cells has been limited because they are very few (450 in each mouse retina, 0.005% of retinal neurons). Here, we applied transgenic technology, single-cell global mRNA amplification, and cDNA...
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.0400913101
更新日期:2004-04-06 00:00:00
abstract::Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves 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.1802354115
更新日期:2018-05-08 00:00:00
abstract::The ecological niche is a key concept for elucidating patterns of species distributions and developing strategies for conserving biodiversity. However, recent times are seeing a widespread debate whether species niches are conserved across space and time (niche conservatism hypothesis). Biological invasions represent ...
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.2004289117
更新日期:2020-09-22 00:00:00
abstract::An understanding of the division of labor in different societies, and especially how it evolved in the human species, is fundamental to most analyses of social, political, and economic systems. The ability to reconstruct how labor was organized, however, especially in ancient societies that left behind few material re...
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.1901367116
更新日期:2019-06-18 00:00:00
abstract::In response to vascular injury, vascular smooth muscle cells (VSMCs) may switch from a contractile to a proliferative phenotype thereby contributing to neointima formation. Previous studies showed that the long noncoding RNA (lncRNA) NEAT1 is critical for paraspeckle formation and tumorigenesis by promoting cell proli...
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.1803725115
更新日期:2018-09-11 00:00:00
abstract::In the present study we have observed that interleukin (IL) 1 alpha or IL-1 beta directly induced expression of human immunodeficiency virus (HIV) in the latently infected human promonocytic cell line U1. In addition, IL-1 synergized with IL-6, but not with tumor necrosis factor, in the upregulation of virus expressio...
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.91.1.108
更新日期:1994-01-04 00:00:00
abstract::Current evidence favors the theory that, when the globular motor domain of myosin attaches to actin, the light chain binding domain or "lever arm" rotates, and thereby generates movement of actin filaments. Myosin is uniquely designed for such a role in that a long alpha-helix (approximately 9 nm) extending from the 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.0401699101
更新日期:2004-07-27 00:00:00
abstract::Many interactions in modern human societies are among strangers. Explaining cooperation in such interactions is challenging. The two most prominent explanations critically depend on individuals' willingness to punish defectors: In models of direct punishment, individuals punish antisocial behavior at a personal cost, ...
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.1413170111
更新日期:2014-11-11 00:00:00
abstract::Photolyzed rhodopsin catalyzes the exchange of GTP for FDP bound to a protein in retinal rod outer segments. We previously proposed that the GTP complex of this protein regulates the cyclic GMP phosphodiesterase and that it may be the first amplified intermediate in visual excitation [Fung, B. K.-K. & Stryer, L. (1980...
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.78.1.152
更新日期:1981-01-01 00:00:00
abstract::The role of ornithine decarboxylase (OrnDCase, EC 4.1.1.17) and of the polyamines [putrescine (Put), spermidine (Spd), and spermine (Spm)] in mouse skin tumor promotion was investigated by the use of alpha-difluoromethylornithine (CHF2-Orn), an enzyme-activated irreversible inhibitor of OrnDCase. 12-O-Tetradecanoylpho...
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.79.19.6028
更新日期:1982-10-01 00:00:00
abstract::A gene's expression pattern provides clues to its role in normal physiology and disease. To provide quantitative expression levels on a genome-wide scale, the Cancer Genome Anatomy Project (CGAP) uses serial analysis of gene expression (SAGE). Over 5 million transcript tags from more than 100 human cell types have bee...
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.152324199
更新日期:2002-08-20 00:00:00
abstract::The rat brain-derived neurotropic factor (BDNF) gene consists of four 5' exons linked to separate promoters and one 3' exon encoding the prepro-BDNF protein. To gain insights into the regulation of BDNF mRNA expression, probes specific for the different 5' exons were used to study the expression of BDNF mRNA in the br...
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.90.19.8802
更新日期:1993-10-01 00:00:00
abstract::The p53 protein is an attractive target for immunotherapy, because mutations in the p53 gene are the most common genetic alterations found in human tumors. These mutations result in high levels of p53 protein in the tumor cell, whereas the expression level of wild-type p53 in nonmalignant tissue is usually much lower....
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.93.10.4781
更新日期:1996-05-14 00:00:00