Abstract:
:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen-regulated gene in the prostate. Supporting a role for sex hormones, males relative to females are disproportionately affected by COVID-19 in terms of mortality and morbidity. Several studies, including one employing a large epidemiological cohort, suggested that blocking androgen signaling is protective against COVID-19. Here, we demonstrate that androgens regulate the expression of ACE2, TMPRSS2, and androgen receptor (AR) in subsets of lung epithelial cells. AR levels are markedly elevated in males relative to females greater than 70 y of age. In males greater than 70 y old, smoking was associated with elevated levels of AR and ACE2 in lung epithelial cells. Transcriptional repression of the AR enhanceosome with AR or bromodomain and extraterminal domain (BET) antagonists inhibited SARS-CoV-2 infection in vitro. Taken together, these studies support further investigation of transcriptional inhibition of critical host factors in the treatment or prevention of COVID-19.
journal_name
Proc Natl Acad Sci U S Aauthors
Qiao Y,Wang XM,Mannan R,Pitchiaya S,Zhang Y,Wotring JW,Xiao L,Robinson DR,Wu YM,Tien JC,Cao X,Simko SA,Apel IJ,Bawa P,Kregel S,Narayanan SP,Raskind G,Ellison SJ,Parolia A,Zelenka-Wang S,McMurry L,Su F,Wang R,doi
10.1073/pnas.2021450118subject
Has Abstractpub_date
2020-12-11 00:00:00eissn
0027-8424issn
1091-6490pii
2021450118pub_type
杂志文章abstract::Closed and pH-tight membrane vesicles prepared from hypocotyls of 5-day-old dark-grown seedlings of Cucurbita pepo accumulate the plant growth hormone indole-3-acetic acid along an imposed proton gradient (pH low outside, high inside). The use of electron paramagnetic spin probes permitted quantitation both of apparen...
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.82.19.6541
更新日期:1985-10-01 00:00:00
abstract::The sequence of a nucleotide region of f1 bacteriophage was determined on a bonded ultrathin acrylamide gel with a discontinuous buffer system by using the dideoxy-DNA sequencing method. This sequence and one other were analyzed for maximal base pairing with tRNAs. The results allow a prediction of the direction and 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.77.6.3539
更新日期:1980-06-01 00:00:00
abstract::Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are central mediators of cardiac hypertrophy and are discussed as potential therapeutic targets. However, direct inhibition of ERK1/2 leads to exacerbated cardiomyocyte death and impaired heart function. We have previously identified ERK(Thr188) autophosphorylati...
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.1221999110
更新日期:2013-04-30 00:00:00
abstract::Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal, a homologue of the p50 and p65 components of NF-kappa B. We describe experiments in yeast with various Dorsal and Cactus derivatives showing that Cactus blocks the DNA binding and nuclear localization functions of Dorsal. In contrast, Dorsal'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.92.22.10242
更新日期:1995-10-24 00:00:00
abstract::Upon stimulation with anti-CD3, suppressor T-cell (Ts) hybridomas and homologous transfectants of T-cell receptor a (TCRalpha) cDNA in the T-cell hybridoma formed a 55-kDa TCRalpha chain derivative that bound both the monoclonal anti-TCRalpha chain and polyclonal antibodies against glycosylation inhibiting factor (GIF...
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.93.14.7207
更新日期:1996-07-09 00:00:00
abstract::Chromosome movement during mitosis is powered in part by energy released through the depolymerization of kinetochore microtubules (MTs). Strong but indirect evidence suggests the existence of a specialized coupling between kinetochores and MT plus ends that enables this transduction of chemical energy into mechanical ...
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.0501142102
更新日期:2005-03-22 00:00:00
abstract::Small ubiquitin modifier 1 (SUMO1) is shown to regulate K2P1 background channels in the plasma membrane (PM) of live mammalian cells. Confocal microscopy reveals native SUMO1, SAE1, and Ubc9 (the enzymes that activate and conjugate SUMO1) at PM where SUMO1 and expressed human K2P1 are demonstrated to colocalize. Silen...
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.1004712107
更新日期:2010-06-08 00:00:00
abstract::On the basis of earlier energy computations, the various single peptide units in proteins were designated as helix-making or helix-breaking.(1) With the use of these designations, empirical rules for distinguishing between alpha-helical and non-alpha-helical regions of proteins have been formulated. These rules includ...
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.62.1.14
更新日期:1969-01-01 00:00:00
abstract::A common genetic mutation found in clear cell renal cell carcinoma (CC-RCC) is the loss of the von Hippel-Lindau (VHL) gene, which results in stabilization of hypoxia-inducible factors (HIFs), and contributes to cancer progression and metastasis. CUB-domain-containing protein 1 (CDCP1) was shown to promote metastasis ...
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.1011777108
更新日期:2011-02-01 00:00:00
abstract::Plants can defend themselves from herbivorous insects by emitting volatile chemical signals that attract natural enemies of the herbivore. For example, maize seedlings attacked by beet armyworm larvae (Spodoptera exigua) produce a mixture of terpenoid and indole volatiles that serve to attract parasitic wasps. A key 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.240284097
更新日期:2000-12-19 00:00:00
abstract::Despite their importance for biological activity, slower molecular motions beyond the nanosecond range remain poorly understood. We have assembled an unprecedented set of experimental NMR data, comprising up to 27 residual dipolar couplings per amino acid, to define the nature and amplitude of backbone motion in 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.0505129102
更新日期:2005-09-27 00:00:00
abstract::The mechanosensory hair cells of the inner ear are required for hearing and balance and have a distinctive apical structure, the hair bundle, that converts mechanical stimuli into electrical signals. This structure comprises a single cilium, the kinocilium, lying adjacent to an ensemble of actin-based projections know...
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.1719861115
更新日期:2018-08-14 00:00:00
abstract::The 5'-terminal triphosphate of the 35S RNA isolated from Rous sarcoma virus is blocked by 7-methylguanosine in 5' linkage with the penultimate nucleoside which is methylated in the 2'-O-ribose position, a type of endgroup found in all animal mRNAs investigated during the past year. The specific nuclease-resistant ter...
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.72.9.3347
更新日期:1975-09-01 00:00:00
abstract::The subdivision of all the experimental days of the Whitetop project into two approximately equal groups, group W with predominantly westerly winds aloft and group E with frequent easterly winds, shows a remarkable difference in the apparent effect of seeding. On W days there was no detectable effect of seeding on rai...
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.64.3.810
更新日期:1969-11-01 00:00:00
abstract::A cDNA library derived from human cerebral cortex was screened for the presence of sodium channel alpha subunit-specific clones. Ligation of three overlapping clones generated a full-length cDNA clone, HBA, that provided the complete nucleotide sequence coding for a protein of 2005 amino acids. The predicted structure...
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.89.17.8220
更新日期:1992-09-01 00:00:00
abstract::A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic...
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.1304888110
更新日期:2013-07-23 00:00:00
abstract::Evidence is presented for the simultaneous release of platelet-activating factor (PAF-acether) and of its deacetylated derivative (lyso-PAF-acether) from hog leukocytes. On the basis of spectroscopy and chemical reactions, the structure of O-deacetyl-PAF is shown to be 1-O-alkylglyceryl 3-phosphorylcholine, an alkyl 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.77.12.7019
更新日期:1980-12-01 00:00:00
abstract::Relatively little is known about the biochemical mechanisms through which the Epstein-Barr virus latent infection integral membrane protein 1 (LMP1) transmembrane domains cause constitutive LMP1 aggregation and continuous cytoplasmic C terminus-mediated signal transduction. We now evaluate the role of the three consec...
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.2237224100
更新日期:2004-01-06 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::Here we study the effects of many-body interactions on rate and mechanism in protein folding by using the results of molecular dynamics simulations on numerous coarse-grained Calpha-model single-domain proteins. After adding three-body interactions explicitly as a perturbation to a Gō-like Hamiltonian with native pair...
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.0403486101
更新日期:2004-10-19 00:00:00
abstract::We have isolated, by molecular cloning and genetic complementation of a listeriolysin-negative mutant, a gene required for the expression of this virulence factor in Listeria monocytogenes. The mutant strain SLCC53, which was nonhemolytic and avirulent, harbored a deletion of 450 base pairs located approximately 1500 ...
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.87.21.8336
更新日期:1990-11-01 00:00:00
abstract::Recent scholarship suggests that the genomes of those around us affect our own phenotypes. Much of the empirical evidence for such "metagenomic" effects comes from animal studies, where the socio-genetic environment can be easily manipulated. Among humans, it is more difficult to identify such effects given the nonran...
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.1806901116
更新日期:2019-08-13 00:00:00
abstract::Neural crest stem cells can be isolated from differentiated cultures of human pluripotent stem cells, but the process is inefficient and requires cell sorting to obtain a highly enriched population. No specific method for directed differentiation of human pluripotent cells toward neural crest stem cells has yet been 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.1113746108
更新日期:2011-11-29 00:00:00
abstract::In vitro data show that the adenomatous polyposis coli (APC) protein associates with the mitotic spindle and that mouse embryonic stem cells with biallelic Apc mutations are karyotypically unstable. These findings led to suggestions that APC acts in chromosomal segregation and that APC inactivation leads to chromosoma...
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.012679099
更新日期:2002-12-24 00:00:00
abstract::HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. Th...
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.86.18.7113
更新日期:1989-09-01 00:00:00
abstract::We report a comprehensive cartography of selective responses to visual letters and words in the human ventral occipito-temporal cortex (VOTC) with direct neural recordings, clarifying key aspects of the neural basis of reading. Intracerebral recordings were performed in a large group of patients (n = 37) presented wit...
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.1718987115
更新日期:2018-08-07 00:00:00
abstract::The template for transcription and replication of negative-stranded RNA viruses is a ribonucleoprotein structure, the nucleocapsid. We have developed a system that supports assembly of the negative-stranded RNA genome of a defective interfering (DI) particle of vesicular stomatitis virus (VSV) into a nucleocapsid in v...
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.85.20.7511
更新日期:1988-10-01 00:00:00
abstract::It has recently been recognized that human serum contains a protein that specifically binds human growth hormone (hGH). This protein has the same restricted specificity for hGH as the membrane-bound GH receptor. To determine whether the GH-binding protein is a derivative of, or otherwise related to, the GH receptor, 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.84.13.4636
更新日期:1987-07-01 00:00:00
abstract::Aortic endothelial cells from normal pigs and pigs with von Willebrand disease have been established in long-term cultures. Both cultures appeared similar in terms of general growth characteristics, morphologic features and ultrastructure. Immunofluorescent staining of these cultures with chicken (or rabbit) antiporci...
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.74.12.5702
更新日期:1977-12-01 00:00:00
abstract::We have studied the reaction dynamics for HgI(2) in methanol by using time-resolved x-ray diffraction (TRXD). Although numerous time-resolved spectroscopic studies have provided ample information about the early dynamics of HgI(2), a comprehensive reaction mechanism in the solution phase spanning from picoseconds up 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.0601958103
更新日期:2006-06-20 00:00:00