Abstract:
:The nuclear receptors LXRalpha and LXRbeta have been implicated in the control of cholesterol and fatty acid metabolism in multiple cell types. Activation of these receptors stimulates cholesterol efflux in macrophages, promotes bile acid synthesis in liver, and inhibits intestinal cholesterol absorption, actions that would collectively be expected to reduce atherosclerotic risk. However, synthetic LXR ligands have also been shown to induce lipogenesis and hypertriglyceridemia in mice, raising questions as to the net effects of these compounds on the development of cardiovascular disease. We demonstrate here that the nonsteroidal LXR agonist GW3965 has potent antiatherogenic activity in two different murine models. In LDLR(-/-) mice, GW3965 reduced lesion area by 53% in males and 34% in females. A similar reduction of 47% was observed in male apoE(-/-) mice. Long-term (12-week) treatment with LXR agonist had differential effects on plasma lipid profiles in LDLR(-/-) and apoE(-/-) mice. GW3965 induced expression of ATP-binding cassettes A1 and G1 in modified low-density lipoprotein-loaded macrophages in vitro as well as in the aortas of hyperlipidemic mice, suggesting that direct actions of LXR ligands on vascular gene expression are likely to contribute to their antiatherogenic effects. These observations provide direct evidence for an atheroprotective effect of LXR agonists and support their further evaluation as potential modulators of human cardiovascular disease.
journal_name
Proc Natl Acad Sci U S Aauthors
Joseph SB,McKilligin E,Pei L,Watson MA,Collins AR,Laffitte BA,Chen M,Noh G,Goodman J,Hagger GN,Tran J,Tippin TK,Wang X,Lusis AJ,Hsueh WA,Law RE,Collins JL,Willson TM,Tontonoz Pdoi
10.1073/pnas.112059299keywords:
subject
Has Abstractpub_date
2002-05-28 00:00:00pages
7604-9issue
11eissn
0027-8424issn
1091-6490journal_volume
99pub_type
杂志文章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::The ever-increasing global need for potable water requires practical, sustainable approaches for purifying abundant alternative sources such as seawater, high-salinity processed water, or underground reservoirs. Evaporation-based solutions are of particular interest for treating high salinity water, since conventional...
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.1905311116
更新日期:2019-07-02 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::The modern Old World Monkeys (Superfamily Cercopithecoidea, Family Cercopithecidae) can be traced back into the late Miocene, but their origin and subsequent diversification is obscured by the scarcity of terrestrial fossil sites in Africa between 15 and 6 Ma. Here, we document the presence of cercopithecids at 12.5 M...
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.1213691110
更新日期:2013-04-09 00:00:00
abstract::Microprocessor [Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) complex] processing of primary microRNA (pri-miRNA) is the critical first step in miRNA biogenesis, but how the Drosha cleavage site is determined has been unclear. Previous models proposed that the Drosha-DGCR8 complex measures either ~22 nt from...
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.1311639110
更新日期:2013-12-17 00:00:00
abstract::AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target e...
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.1405186111
更新日期:2014-08-05 00:00:00
abstract::Sleep is essential for basic survival, and insufficient sleep leads to a variety of dysfunctions. In humans, one of the most profound consequences of sleep deprivation is imprecise or irrational communication, demonstrated by degradation in signaling as well as in receiving information. Communication in nonhuman anima...
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.1009439108
更新日期:2010-12-28 00:00:00
abstract::Complex liquids flow through channels faster than expected, an effect attributed to the formation of low-viscosity depletion layers at the boundaries. Characterization of depletion layer length scale, concentration, and dynamics has remained elusive due in large part to the lack of suitable real-space experimental tec...
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.1900623116
更新日期:2019-08-13 00:00:00
abstract::Climate change due to anthropogenic greenhouse gas emissions is expected to increase the frequency and intensity of precipitation events, which is likely to affect the probability of flooding into the future. In this paper we use river flow simulations from nine global hydrology and land surface models to explore unce...
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.1302078110
更新日期:2014-03-04 00:00:00
abstract::Smallpox has played an unparalleled role in human history and remains a significant potential threat to public health. Despite the historical significance of this disease, we know little about the underlying pathophysiology or the virulence mechanisms of the causative agent, variola virus. To improve our understanding...
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.0405759101
更新日期:2004-10-19 00:00:00
abstract::The powerful optogenetic pharmacology method allows the optical control of neuronal activity by photoswitchable ligands tethered to channels and receptors. However, this approach is technically demanding, as it requires the design of pharmacologically active ligands. The development of versatile technologies therefore...
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.1318715110
更新日期:2013-12-17 00:00:00
abstract::Intergroup conflict is a persistent feature of many human societies yet little is known about why individuals participate when doing so imposes a mortality risk. To evaluate whether participation in warfare is associated with reproductive benefits, we present data on participation in small-scale livestock raids among ...
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.1412287112
更新日期:2015-01-13 00:00:00
abstract::Carrying premature termination codons in 1 allele of the ABCA7 gene is associated with an increased risk for Alzheimer's disease (AD). While the primary function of ABCA7 is to regulate the transport of phospholipids and cholesterol, ABCA7 is also involved in maintaining homeostasis of the immune system. Since inflamm...
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.1908529116
更新日期:2019-11-19 00:00:00
abstract::Interferon γ-inducible protein 16 (IFI16) and cGMP-AMP synthase (cGAS) have both been proposed to detect herpesviral DNA directly in herpes simplex virus (HSV)-infected cells and initiate interferon regulatory factor-3 signaling, but it has been unclear how two DNA sensors could both be required for this response. We ...
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.1424637112
更新日期:2015-04-07 00:00:00
abstract::Pregnant mothers often report a special awareness of and bonding with their unborn child. Little is known about this relationship although it may offer potential for the assessment of the fetal condition. Recently we found evidence of short epochs of fetal-maternal heart rate synchronization under uncontrolled conditi...
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.0901049106
更新日期:2009-08-18 00:00:00
abstract::Human telomeres terminate with a single-stranded 3' G overhang, which can be recognized as a DNA damage site by replication protein A (RPA). The protection of telomeres (POT1)/POT1-interacting protein 1 (TPP1) heterodimer binds specifically to single-stranded telomeric DNA (ssTEL) and protects G overhangs against RPA ...
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.1321436111
更新日期:2014-02-25 00:00:00
abstract::We have measured the angle-resolved transverse resistivity (ARTR), a sensitive indicator of electronic anisotropy, in high-quality thin films of the unconventional superconductor Sr2RuO4 grown on various substrates. The ARTR signal, heralding the electronic nematicity or a large nematic susceptibility, is present and ...
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.1921713117
更新日期:2020-05-19 00:00:00
abstract::Two-dimensional Raman-terahertz (THz) spectroscopy is presented as a multidimensional spectroscopy directly in the far-IR regime. The method is used to explore the dynamics of the collective intermolecular modes of liquid water at ambient temperatures that emerge from the hydrogen-bond networks water forming. Two-dime...
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.1317459110
更新日期:2013-12-17 00:00:00
abstract::Murine Ly-6-encoded molecules play an important role in the antigen-independent activation of lymphocytes. We have described the cloning of a cDNA encoding the protein component of an Ly-6 molecule. Hybridization studies indicated that this cDNA identified multiple DNA fragments on Southern blots. The banding pattern ...
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.84.6.1638
更新日期:1987-03-01 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::Mosquitoes transmit devastating human diseases because they need vertebrate blood for egg development. Metabolism in female mosquitoes is tightly coupled with blood meal-mediated reproduction, which requires an extremely high level of energy consumption. Functional analysis has shown that major genes encoding for enzy...
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.1619326114
更新日期:2017-03-28 00:00:00
abstract::The method presented here refines molecular conformations directly against projections of single particles measured by electron microscopy. By optimizing the orientation of the projection at the same time as the conformation, the method is well-suited to two-dimensional class averages from cryoelectron microscopy. Suc...
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.1205945109
更新日期:2012-06-19 00:00:00
abstract::Nucleotide excision repair proteins have been implicated in genetic recombination by experiments in Saccharomyces cerevisiae and Drosophila melanogaster, but their role, if any, in mammalian cells is undefined. To investigate the role of the nucleotide excision repair gene ERCC1, the hamster homologue to the S. cerevi...
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.94.24.13122
更新日期:1997-11-25 00:00:00
abstract::Transformation promotes genome plasticity in bacteria via RecA-driven homologous recombination. In the gram-positive human pathogen Streptococcus pneumoniae, the transformasome a multiprotein complex, internalizes, protects, and processes transforming DNA to generate chromosomal recombinants. Double-stranded DNA is 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.1205638109
更新日期:2012-09-11 00:00:00
abstract::Tata Element Modulatory Factor (TMF/ARA160) is a multifunctional Golgi-associated protein, which accumulates in colonic enterocytes and goblet cells. Mice lacking TMF/ARA160 (TMF(-/-)) produce thick and uniform colonic mucus that resists adherent bacterial colonization and diminishes susceptibility of these mice to 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.1319114111
更新日期:2014-04-01 00:00:00
abstract::The intracellular signaling mechanisms regulating the generation and long-term persistence of memory T cells in vivo remain unclear. In this study, we used mouse models with conditional deletion of the key T cell receptor (TCR)-coupled adaptor molecule SH2-domain-containing phosphoprotein of 76 kDa (SLP-76), to analyz...
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.0908126107
更新日期:2010-01-12 00:00:00
abstract::alpha-1-Antitrypsin is a serum protein that inhibits many proteolytic enzymes. Recently, it was suggested that the alpha-1-antitrypsin-trypsin complex is an acyl ester analogous to the acyl intermediate that forms between trypsin and its substrates. In previous work we showed that the alpha-1-antitrypsin-trypsin compl...
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.74.10.4311
更新日期:1977-10-01 00:00:00
abstract::Optical imaging of the functional architecture of cortex, based on intrinsic signals, is a useful tool for the study of the development, organization, and function of the living mammalian brain. This relatively noninvasive technique is based on small activity-dependent changes of the optical properties of cortex. Thus...
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.88.24.11559
更新日期:1991-12-15 00:00:00
abstract::RNA interference (RNAi) is triggered in eukaryotic organisms by double-stranded RNA (dsRNA), and it destroys any mRNA that has sequence identity with the dsRNA trigger. The RNAi pathway in Anopheles gambiae can be silenced by transfecting cells with dsRNA derived from exon sequence of the A. gambiae Argonaute2 (AgAgo2...
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.0406983101
更新日期:2004-12-07 00:00:00
abstract::Deciding whether a set of objects are the same or different is a cornerstone of perception and cognition. Surprisingly, no principled quantitative model of sameness judgment exists. We tested whether human sameness judgment under sensory noise can be modeled as a form of probabilistically optimal inference. An optimal...
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.1108790109
更新日期:2012-02-21 00:00:00