Abstract:
:Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea and HIV. Neisseria gonorrhoeae, which causes gonorrhea, is particularly adept at driving HIV-1 expression, but the molecular determinants of this relationship remain undefined. N. gonorrhoeae liberates a soluble factor that potently induces expression from the HIV-1 LTR in coinfected cluster of differentiation 4-positive (CD4(+)) T lymphocytes, but this factor is not a previously described innate effector. A genome-wide mutagenesis approach was undertaken to reveal which component(s) of N. gonorrhoeae induce HIV-1 expression in CD4(+) T lymphocytes. A mutation in the ADP-heptose biosynthesis gene, hldA, rendered the bacteria unable to induce HIV-1 expression. The hldA mutant has a truncated lipooligosaccharide structure, contains lipid A in its outer membrane, and remains bioactive in a TLR4 reporter-based assay but did not induce HIV-1 expression. Mass spectrometry analysis of extensively fractionated N. gonorrhoeae-derived supernatants revealed that the LTR-inducing fraction contained a compound having a mass consistent with heptose-monophosphate (HMP). Heptose is a carbohydrate common in microbes but is absent from the mammalian glycome. Although ADP-heptose biosynthesis is common among Gram-negative bacteria, and heptose is a core component of most lipopolysaccharides, N. gonorrhoeae is peculiar in that it effectively liberates HMP during growth. This N. gonorrhoeae-derived HMP activates CD4(+) T cells to invoke an NF-κB-dependent transcriptional response that drives HIV-1 expression and viral production. Our study thereby shows that heptose is a microbial-specific product that is sensed as an innate immune agonist and unveils the molecular link between N. gonorrhoeae and HIV-1.
journal_name
Proc Natl Acad Sci U S Aauthors
Malott RJ,Keller BO,Gaudet RG,McCaw SE,Lai CC,Dobson-Belaire WN,Hobbs JL,St Michael F,Cox AD,Moraes TF,Gray-Owen SDdoi
10.1073/pnas.1303738110subject
Has Abstractpub_date
2013-06-18 00:00:00pages
10234-9issue
25eissn
0027-8424issn
1091-6490pii
1303738110journal_volume
110pub_type
杂志文章abstract::The transcription factor cAMP response element (CRE)-binding protein (CREB) has been shown to regulate neural plasticity. Drugs of abuse activate CREB in the nucleus accumbens, an important part of the brain's reward pathways, and local manipulations of CREB activity have been shown to affect cocaine reward, suggestin...
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.172091899
更新日期:2002-08-20 00:00:00
abstract::Recombinant, replication-competent rabies virus (RV) vaccine strain-based vectors were developed expressing HIV type I (HIV-1) envelope glycoprotein (gp160) from both a laboratory-adapted (CXCR4-tropic) and a primary (dual-tropic) HIV-1 isolate. An additional transcription stop/start unit within the RV genome was used...
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.050589197
更新日期:2000-03-28 00:00:00
abstract::Transcription of the type 1 herpes simplex virus (HSV-1) genome in trigeminal ganglia of latently infected mice was studied using in situ hybridization. Probes representative of each temporal gene class were used to determine the regions of the genome that encode the transcripts present in latently infected cells. Pro...
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.84.10.3204
更新日期:1987-05-01 00:00:00
abstract::Skeletal and smooth muscle can mutually transdifferentiate, but little molecular insight exists as to how each muscle program may be subverted to the other. The myogenic basic helix-loop-helix transcription factors MyoD and myogenin (Myog) direct the development of skeletal muscle and are thought to be dominant over 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.0708253104
更新日期:2007-10-16 00:00:00
abstract::Ribozymes are RNAs that possess the dual properties of RNA sequence-specific recognition, analogous to conventional antisense molecules, and RNA substrate destruction via site-specific cleavage. The cleavage reaction is catalytic in that more than one substrate molecule is processed per ribozyme molecule. We have desi...
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.89.22.10802
更新日期:1992-11-15 00:00:00
abstract::Stimulation by isoproterenol causes large increases in the activity of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) after a variable lag period. Lengthening periods of exposure to light cause rapid increases in the sensitivity of pineal N-acetyltr...
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.72.5.1661
更新日期:1975-05-01 00:00:00
abstract::Monovalent antibodies (Fab) directed to two classes of transformation-sensitive cell surface components, ganglioside and galactoprotein a (Gap a), inhibit the process of oncogenic viral transformation of cells. Mouse 3T3 cells infected with murine sarcoma virus were not transformed in terms of morphology change and en...
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.75.12.6049
更新日期:1978-12-01 00:00:00
abstract::Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) were isolated from lysates of human eosinophil granules by gel filtration and ion exchange chromatography on heparin-Sepharose. Radioimmunoassay, using monoclonal antibodies, of fractions from the heparin-Sepharose chromatography showed one peak...
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.83.10.3146
更新日期:1986-05-01 00:00:00
abstract::Control over structural transformations in supramolecular entities by external stimuli is critical for the development of adaptable and functional soft materials. Herein, we have designed and synthesized a dipyridyl donor containing a central Z-configured stiff-stilbene unit that self-assembles in the presence of two ...
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.1408620111
更新日期:2014-06-17 00:00:00
abstract::A fragment of the cloned gene for the human myeloma ND epsilon chain, coding for the second, third, and fourth domains of the immunoglobulin, has been coupled to the tryptophan control region of an expression plasmid and subcloned in Escherichia coli. Induction of gene expression results in the synthesis of the expect...
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.81.10.2955
更新日期:1984-05-01 00:00:00
abstract::Hepatitis E virus is responsible for both sporadic and epidemic hepatitis in developing countries. The nonenveloped virus is 27-34 nm in diameter and has been shown to contain a single-strand, positive-sense, polyadenylylated RNA genome of approximately 7.5 kilobases. The nucleotide sequence of the Burma strain of hep...
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.89.9.3855
更新日期:1992-05-01 00:00:00
abstract::Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalia...
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.77.8.4961
更新日期:1980-08-01 00:00:00
abstract::The quantitative autoradiographic 2-deoxy-[14C]glucose technique has been used with conscious rats to investigate the functional consequences (reflected as alterations in local rates of glucose utilization) of unilateral intrastriatal administration of vasoactive intestinal polypeptide. Intrastriatal administration 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.80.5.1472
更新日期:1983-03-01 00:00:00
abstract::Regulatory T cells (Tregs) are key modulators of immune tolerance, capable of suppressing inflammatory immune responses and promoting nonlymphoid tissue homeostasis. Helios, a transcription factor (TF) that is selectively expressed by Tregs, has been shown to be essential for the maintenance of Treg lineage stability ...
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.1720447115
更新日期:2018-02-27 00:00:00
abstract::Tissue kallikrein (TK) is a serine protease synthetized in renal tubular cells located upstream from the collecting duct where renal potassium balance is regulated. Because secretion of TK is promoted by K+ intake, we hypothesized that this enzyme might regulate plasma K+ concentration ([K+]). We showed in wild-type 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.0913070107
更新日期:2010-07-27 00:00:00
abstract::The heat shock protein (Hsp)70 family of molecular chaperones interacts with unfolded proteins through a C-terminal substrate-binding domain (SBD) that is controlled by nucleotide binding to the N-terminal domain. The ATPase cycle is regulated by cochaperones, including DnaJ proteins that accelerate ATP hydrolysis to ...
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.0702132105
更新日期:2008-01-29 00:00:00
abstract::In a study of autonomic reflexes it was found that some produce a generalized, bilaterally uniform response whereas others have an asymmetric or laterality of action. Recordings from vertebral nerve fibers (mainly vasoconstrictors to forelimb muscles), right and left cardiac sympathetics, and renal nerves show that ba...
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.75.10.5239
更新日期:1978-10-01 00:00:00
abstract::We have isolated, cloned, and expressed a male antennae-specific pheromone-degrading enzyme (PDE) [Antheraea polyphemus PDE (ApolPDE), formerly known as Sensillar Esterase] from the wild silkmoth, A. polyphemus, which seems essential for the rapid inactivation of pheromone during flight. The onset of enzymatic activit...
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.0505340102
更新日期:2005-09-27 00:00:00
abstract::Given the widely noted increase in the warming effects of rising greenhouse gas concentrations, it has been unclear why global surface temperatures did not rise between 1998 and 2008. We find that this hiatus in warming coincides with a period of little increase in the sum of anthropogenic and natural forcings. Declin...
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.1102467108
更新日期:2011-07-19 00:00:00
abstract::Spontaneous cross-linking in vitro, during incubation of purified collagen in nonstriated and native type fibrils, was studied to elucidate the relationship between intra and intermolecular cross-links. In nonbanded fibrils, the aldol condensation products of two allysyl residues, previously shown to constitute the 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.67.3.1307
更新日期:1970-11-01 00:00:00
abstract::In the present article we describe the design and evaluation of a synthetic receptor that binds to the exterior surface of chymotrypsin and disrupts its interaction with proteinaceous inhibitors, such as soybean trypsin inhibitor, basic pancreatic trypsin inhibitor, ovomucoid turkey inhibitor, and Bowman-Birk inhibito...
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.082675899
更新日期:2002-04-16 00:00:00
abstract::Experimental work in animals has shown that memory formation depends on a cascade of molecular events. Here we show that variability of human memory performance is related to variability in genes encoding proteins of this signaling cascade, including the NMDA and metabotrobic glutamate receptors, adenylyl cyclase, CAM...
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.0510212103
更新日期:2006-03-14 00:00:00
abstract::Two human B-cell differentiation antigens, Bp35 and Bp50, apparently play distinct roles as signal receptors in B-cell activation. Monoclonal antibodies (mAbs) to either Bp35 or Bp50 deliver positive signals to B cells that stimulate their transition through the cell cycle. mAb to Bp35, like anti-immunoglobulin antibo...
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.83.12.4494
更新日期:1986-06-01 00:00:00
abstract::Large quantities of mineral dust particles are frequently ejected into the atmosphere through the action of wind. The surface of dust particles acts as a sink for many gases, such as sulfur dioxide. It is well known that under most conditions, sulfur dioxide reacts on dust particle surfaces, leading to the production ...
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.1212297109
更新日期:2012-12-18 00:00:00
abstract::PCR was used to isolate nucleotide sequences that may encode novel members of the neuropeptide Y receptor family. By use of a PCR product as a hybridization probe, a full-length human cDNA was isolated that encodes a 375-aa protein with a predicted membrane topology identifying it as a member of the G-protein-coupled ...
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.93.10.4661
更新日期:1996-05-14 00:00:00
abstract::Human low density lipoproteins (LDL) are the major cholesterol carriers in the blood. Elevated concentration of LDL is a major risk factor for atherosclerotic disease. Purified LDL particles appear heterogeneous in images obtained with a 400-kV electron cryomicroscope. Using multivariate statistical and cluster analys...
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.96.15.8420
更新日期:1999-07-20 00:00:00
abstract::Two monoclonal antibodies directed against the native beta 2 subunit of Escherichia coli tryptophan synthase [L-serine hydro-lyase (adding indoleglycerol-phosphate), EC 4.2.1.20], one recognizing the C-terminal F1 domain and the other the N-terminal F2 domain, were used to detect immunoreactive intermediates in the fo...
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.84.5.1147
更新日期:1987-03-01 00:00:00
abstract::Equine arteritis virus (EAV) is a positive-strand RNA virus that uses a discontinuous transcription mechanism to generate a nested set of six subgenomic mRNAs from which its structural genes are expressed. A stable bacterial plasmid (pEAV030) containing a full-length cDNA copy of the 12.7-kb EAV genome was constructed...
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.94.3.991
更新日期:1997-02-04 00:00:00
abstract::A form of autosomal dominant juvenile myoclonic epilepsy is caused by a nonconservative missense mutation, A322D, in the GABAA receptor alpha1 subunit M3 transmembrane helix. We reported previously that the A322D mutation reduced total and surface alpha1(A322D) subunit protein and that residual alpha1(A322D) subunit 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.0700163104
更新日期:2007-08-07 00:00:00
abstract::The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo 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.1821370116
更新日期:2019-05-07 00:00:00