Abstract:
:To identify genetic factors that interact with social environments to impact human health, we used a bioinformatic strategy that couples expression array-based detection of environmentally responsive transcription factors with in silico discovery of regulatory polymorphisms to predict genetic loci that modulate transcriptional responses to stressful environments. Tests of one predicted interaction locus in the human IL6 promoter (SNP rs1800795) verified that it modulates transcriptional response to beta-adrenergic activation of the GATA1 transcription factor in vitro. In vivo validation studies confirmed links between adverse social conditions and increased transcription of GATA1 target genes in primary neural, immune, and cancer cells. Epidemiologic analyses verified the health significance of those molecular interactions by documenting increased 10-year mortality risk associated with late-life depressive symptoms that occurred solely for homozygous carriers of the GATA1-sensitive G allele of rs1800795. Gating of depression-related mortality risk by IL6 genotype pertained only to inflammation-related causes of death and was associated with increased chronic inflammation as indexed by plasma C-reactive protein. Computational modeling of molecular interactions, in vitro biochemical analyses, in vivo animal modeling, and human molecular epidemiologic analyses thus converge in identifying beta-adrenergic activation of GATA1 as a molecular pathway by which social adversity can alter human health risk selectively depending on individual genetic status at the IL6 locus.
journal_name
Proc Natl Acad Sci U S Aauthors
Cole SW,Arevalo JM,Takahashi R,Sloan EK,Lutgendorf SK,Sood AK,Sheridan JF,Seeman TEdoi
10.1073/pnas.0911515107subject
Has Abstractpub_date
2010-03-23 00:00:00pages
5681-6issue
12eissn
0027-8424issn
1091-6490pii
0911515107journal_volume
107pub_type
杂志文章abstract::The growth of 3T3 and SV101 3T3 cells in a lipid-depleted medium is enhanced by the addition of biotin or some fatty acids. The extent of enhancement depends on the fatty acid(s) supplied. The presence of linoleate is unique, since it induces a morphological alteration in 3T3 cells resulting in a cell similar to an SV...
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.71.8.3115
更新日期:1974-08-01 00:00:00
abstract::Cytosine methylation at CpG dinucleotides contributes to the epigenetic maintenance of gene silencing. Dynamic reprogramming of DNA methylation patterns is believed to play a key role during development and differentiation in vertebrates. The mechanisms of DNA demethylation remain unclear and controversial. Here, we 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.0601793103
更新日期:2006-07-25 00:00:00
abstract::The AG dinucleotide at the 3' splice sites of metazoan nuclear pre-mRNAs plays a critical role in catalytic step II of the splicing reaction. Previous studies have shown that replacement of the guanine by adenine in the AG (AG --> GG) inhibits this step. We find that the second step was even more severely inhibited by...
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.97.1.115
更新日期:2000-01-04 00:00:00
abstract::Plasmid pT181 is a 4437-base-pair, multicopy plasmid of Staphylococcus aureus that encodes tetracycline resistance. The replication of the leading strand of pT181 DNA initiates by covalent extension of a site-specific nick generated by the initiator protein at the origin of replication and proceeds by an asymmetric ro...
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.89.1.290
更新日期:1992-01-01 00:00:00
abstract::Histone H3 phosphorylation is a critical step that couples signal transduction pathways to gene regulation. To specifically assess the transcriptional regulatory functions of H3 phosphorylation, we developed an in vivo targeting approach and found that the H3 kinase MSK1 is a direct and potent transcriptional activato...
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.1012798108
更新日期:2011-02-15 00:00:00
abstract::Studies on contact-inhibited mouse embryo fibroblast 3T3 cells and 3T3 cells transformed by oncogenic RNA and DNA viruses and by a chemical carcinogen have demonstrated differences in plasma membrane architecture. Spin-label and freeze-fracture ultrastructural studies have shown that contact-inhibited cells have order...
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.71.5.1992
更新日期:1974-05-01 00:00:00
abstract::Hexamethylene bisacetamide (HMBA) induces in vitro the cytodifferentiation of PCC3/A/1 mouse embryonal carcinoma (EC) cells. In EC cells, actin is associated with surface structures but microfilament bundles are not seen. After 2 days of HMBA treatment, rounded EC cells are converted to flat adhesive ones with a devel...
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.76.4.1891
更新日期:1979-04-01 00:00:00
abstract::Physical biochemical techniques are used to establish the structure, subunit stoichiometry, and assembly pathway of the primosome complex of the bacteriophage T4 DNA replication system. Analytical ultracentrifugation and fluorescence anisotropy methods show that the functional T4 primosome consists of six gp41 helicas...
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.1210040109
更新日期:2012-08-21 00:00:00
abstract::Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 microM in 2 days and effectively eliminates the parasite in 2-4 days ...
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.96.23.13387
更新日期:1999-11-09 00:00:00
abstract::Peripheral blood leukocytes, obtained from volunteers after vaccination or natural illness with influenza, were assayed for cytotoxicity against influenza virus-infected cells. Approximately 7 days after vaccination or the onset of respiratory illness, peak cytotoxicity was demonstrated in a chromium-release assay. Se...
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.76.9.4622
更新日期:1979-09-01 00:00:00
abstract::We have previously shown that geographic differences in cancer mortalities in Europe are related to (in order of importance): geographic distances (reflecting environmental differences), ethnohistoric distances (encompassing cultural and genetic attributes), and genetic distances of the populations in the areas studie...
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.97.11.6067
更新日期:2000-05-23 00:00:00
abstract::Werner syndrome and Bloom syndrome result from defects in the RecQ helicases Werner (WRN) and Bloom (BLM), respectively, and display premature aging phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1-XPF DNA repair endonuclease. To gain insight into the origin of cellular senescence and hu...
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.1006338107
更新日期:2010-09-07 00:00:00
abstract::Arteriovenous (AV) malformation (AVM) is a devastating condition characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries directly to veins. AVMs can form anywhere in the body and can cause debilitating ischemia and life-threatening hemorrhagic stroke. The mechanisms that underlie AVM...
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.1415316111
更新日期:2014-12-16 00:00:00
abstract::The linear ubiquitin assembly complex (LUBAC) comprises 3 components: HOIP, HOIL-1, and Sharpin, of which HOIP and HOIL-1 are both members of the RBR subfamily of E3 ubiquitin ligases. HOIP catalyses the formation of Met1-linked ubiquitin oligomers (also called linear ubiquitin), but the function of the E3 ligase acti...
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.1905873116
更新日期:2019-07-02 00:00:00
abstract::A genomic clone containing two linked human pregnancy-specific beta 1-glycoprotein (PS beta G) genes has been isolated and characterized. The two genes are arranged in the same 5'----3' orientation; the 3' region (including the A2 and B-C exons) of the upstream gene, PSGGA, is linked to the 5' region (including the 5'...
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.87.15.5822
更新日期:1990-08-01 00:00:00
abstract::It is shown that a stereochemical correspondence between two molecular systems can be represented by a commuting diagram of the point groups and permutation groups involved. The effect of the diagrammatic condition on the mappings of the cosets, double cosets, subgroup lattice, and double coset algebra determined for ...
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.72.6.2385
更新日期:1975-06-01 00:00:00
abstract::TREK channels produce background currents that regulate cell excitability. These channels are sensitive to a wide variety of stimuli including polyunsaturated fatty acids (PUFAs), phospholipids, mechanical stretch, and intracellular acidification. They are inhibited by neurotransmitters, hormones, and pharmacological ...
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.1015788108
更新日期:2011-02-08 00:00:00
abstract::Cooperation via production of common goods is found in diverse life forms ranging from viruses to social animals. However, natural selection predicts a "tragedy of the commons": Cheaters, benefiting from without producing costly common goods, are more fit than cooperators and should destroy cooperation. In an attempt ...
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.1210190109
更新日期:2012-11-20 00:00:00
abstract::Hepatitis C virus (HCV) NS3-4A is a membrane-associated multifunctional protein harboring serine protease and RNA helicase activities. It is an essential component of the HCV replication complex and a prime target for antiviral intervention. Here, we show that membrane association and structural organization of HCV NS...
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.0807298105
更新日期:2008-09-23 00:00:00
abstract::Thymin, a purified polypeptide isolated from bovine thymus, was shown to induce the expression of differentiation antigens characteristic of thymocytes [TL and Thy-1 (theta)] when incubated in vitro with mouse bone marrow or spleen cells. This induction occurred in 5-10% of the cells from bone marrow after a 2-hr incu...
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.71.4.1474
更新日期:1974-04-01 00:00:00
abstract::The surface distributions of three different membrane integral proteins, beta2-microglobulin (part of the histocompatibility antigen complex), aminopeptidase (alpha-aminoacyl-peptide hydrolase; EC 3.4.11.2), and the Na+,K+-ATPase (ATP phosphohydrolase; EC 3.6.1.3) on human fibroblasts grown in monolayer culture have b...
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.74.12.5584
更新日期:1977-12-01 00:00:00
abstract::Lung cancer is the number one cause of cancer-related deaths in the world. Patients treated with current chemotherapies for non-small-cell lung cancers (NSCLCs) have a survival rate of approximately 15% after 5 years. Novel approaches are needed to treat this disease. We show elevated NAD(P)H:quinone oxidoreductase-1 ...
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.0702176104
更新日期:2007-07-10 00:00:00
abstract::Recombination is unknown in natural populations of Rivulus marmoratus, a selfing hermaphrodite, and genetic variation is likely due to mutation alone. DNA fingerprinting with an array of microsatellite [e.g., (CT)9] and minisatellite (e.g., the 33.15 core sequence) probes reveals very high clonal diversity within samp...
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.89.22.10643
更新日期:1992-11-15 00:00:00
abstract::Ras has achieved notoriety as an oncogene aberrantly activated in multiple human tumors. Approximately 30% of all human tumors express an oncogenic form of this GTPase that is locked in an active conformation as a result of being insensitive to Ras GTPase-activating proteins (GAPs), proteins that normally regulate the...
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.0700153104
更新日期:2007-07-24 00:00:00
abstract::Balanced genetic polymorphism has been proposed as a source from which to infer population history complementary to that of neutral genetic polymorphism, because genetic polymorphism maintained by balancing selection permits inferences about population size over much longer spans of time. However, empirical data for b...
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.96.1.168
更新日期:1999-01-05 00:00:00
abstract::Aberrations in the T cell repertoire with the emergence of oligoclonal populations have been described in patients with rheumatoid arthritis (RA). However, the extent of the repertoire perturbations as well as the underlying mechanisms are not known. We now have examined the diversity of the peripheral CD4 T cell repe...
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.95.24.14447
更新日期:1998-11-24 00:00:00
abstract::KRAS mutant tumors are largely recalcitrant to targeted therapies. Genetically engineered mouse models (GEMMs) of Kras mutant cancer recapitulate critical aspects of this disease and are widely used for preclinical validation of targets and therapies. Through comprehensive profiling of exomes and matched transcriptome...
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.1708391114
更新日期:2017-12-19 00:00:00
abstract::The plasmid construct pSVO-CAT has been used to test adenovirus promoter activities in the unmethylated or methylated state. We have now observed that the E2A late promoter of adenovirus type 2 (Ad2) DNA also activated the chloramphenicol acetyltransferase (CAT) gene upon transfection of the pAd2E2A-CAT construct into...
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.83.6.1598
更新日期:1986-03-01 00:00:00
abstract::Normal neural development is essential for the formation of neuronal networks and brain function. Cutaneous T cell lymphoma-associated antigen 5 (cTAGE5)/meningioma expressed antigen 6 (MEA6) plays a critical role in the secretion of proteins. However, its roles in the transport of nonsecretory cellular components 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.1804083115
更新日期:2018-10-02 00:00:00
abstract::Worldwide, 90% of HIV-1 infections are transmitted heterosexually. Because the genital mucosa are the sites of initial contact with HIV-1 for most exposed individuals, study of the virus from the genital tract is critical for the development of vaccines and therapeutics. Previous analyses of HIV-1 in various tissues 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.2134064100
更新日期:2003-10-28 00:00:00