Abstract:
:Genetic variation in the serotonin transporter gene (SLC6A4) is associated with vulnerability to affective disorders and pharmacotherapy efficacy. We recently identified sequence polymorphisms in the common marmoset SLC6A4 repeat region (AC/C/G and CT/T/C) associated with individual differences in anxiety-like trait, gene expression, and response to antidepressants. The mechanisms underlying the effects of these polymorphisms are unknown, but a key mediator of serotonin action is the serotonin 2A receptor (5HT2A). Thus, we correlated 5HT2A binding potential (BP) and RNA gene expression in 16 SLC6A4 genotyped marmosets with responsivity to 5HT2A antagonism during the human intruder test of anxiety. Voxel-based analysis and RNA measurements showed a reduction in 5HT2A BP and gene expression specifically in the right posterior insula of individuals homozygous for the anxiety-related variant AC/C/G. These same marmosets displayed an anxiogenic, dose-dependent response to the human intruder after 5HT2A pharmacological antagonism, while CT/T/C individuals showed no effect. A voxel-based correlation analysis, independent of SLC6A4 genotype, revealed that 5HT2A BP in the adjacent right anterior insula and insula proisocortex was negatively correlated with trait anxiety scores. Moreover, 5HT2A BP in both regions was a good predictor of the size and direction of the acute emotional response to the human intruder threat after 5HT2A antagonism. Our findings suggest that genetic variation in the SLC6A4 repeat region may contribute to the trait anxious phenotype via neurochemical changes in brain areas implicated in interoceptive and emotional processing, with a critical role for the right insula 5HT2A in the regulation of affective responses to threat.
journal_name
Proc Natl Acad Sci U S Aauthors
Santangelo AM,Sawiak SJ,Fryer T,Hong Y,Shiba Y,Clarke HF,Riss PJ,Ferrari V,Tait R,Suckling J,Aigbirhio FI,Roberts ACdoi
10.1073/pnas.1902087116subject
Has Abstractpub_date
2019-07-16 00:00:00pages
14761-14768issue
29eissn
0027-8424issn
1091-6490pii
1902087116journal_volume
116pub_type
杂志文章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::Methylmercury (MeHg) is a potent neurotoxin that is biomagnified approximately 1-10 million-fold in aquatic carnivores such as the Northern elephant seal (Mirounga angustirostris), whose excreta and molted pelage, in turn, constitute a source of environmental MeHg contamination at the base of marine food chains. The 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.1506520112
更新日期:2015-09-29 00:00:00
abstract::Nicks within one strand of the bacteriophage T5 DNA molecule act as " weak points" for a novel kind mechanical breakage that can be utilized for "dissecting" the genome. The products from sheared T5(+) DNA include five unique double-stranded segments of the molecule and various combinations of adjacent segments. These...
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.71.5.2108
更新日期:1974-05-01 00:00:00
abstract::The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.0606053103
更新日期:2006-09-05 00:00:00
abstract::Previous work has established stargazin and its related family of transmembrane AMPA receptor regulatory proteins (TARPs) as auxiliary subunits of AMPA receptors (AMPARs) that control synaptic strength both by targeting AMPARs to synapses through an intracellular PDZ-binding motif and by modulating their gating throug...
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.0905570106
更新日期:2009-07-07 00:00:00
abstract::A way to assess specific CD8+ T-cell activity in a skin test analogous to the conventional delayed-type hypersensitivity (DTH) reaction for CD4+ T cells is presented. Local injection of viral class I binding peptides caused a specific CD8+ T-cell-mediated DTH in footpads of virally infected mice. The DTH was inducible...
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.89.16.7757
更新日期:1992-08-15 00:00:00
abstract::Suppressor T cells have been shown to be much more radiosensitive than other lymphoïd cells, and we have tried to reduce tumor growth by low-dose irradiation. Syngeneic DBA/2 mice received whole-body irradiation (150 rads; 1 rad = 0.01 J/kg) 6 days after P815 tumor inoculation. Tumor growth is significantly reduced 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.78.3.1809
更新日期:1981-03-01 00:00:00
abstract::Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here we describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no...
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.87.14.5383
更新日期:1990-07-01 00:00:00
abstract::Voltage-gated sodium (Na(V)) and potassium (K(V)) channels are critical components of neuronal action potential generation and propagation. Here, we report that Na(V)β1 encoded by SCN1b, an integral subunit of Na(V) channels, coassembles with and modulates the biophysical properties of K(V)1 and K(V)7 channels, but no...
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.1209142109
更新日期:2012-11-06 00:00:00
abstract::The glycine receptor (GlyR) is a pentameric ligand-gated ion channel (pLGIC) mediating inhibitory transmission in the nervous system. Its transmembrane domain (TMD) is the target of allosteric modulators such as general anesthetics and ethanol and is a major locus for hyperekplexic congenital mutations altering the al...
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.1417864112
更新日期:2015-03-03 00:00:00
abstract::One of the strategies used by organisms to adapt to life under conditions of short energy supply is to use the by-product pyrophosphate to support cation gradients in membranes. Transport reactions are catalyzed by membrane-integral pyrophosphatases (PPases), which are classified into two homologous subfamilies: 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.1217816110
更新日期:2013-01-22 00:00:00
abstract::A common challenge in pathogen discovery by deep sequencing approaches is to recognize viral or subviral pathogens in samples of diseased tissue that share no significant homology with a known pathogen. Here we report a homology-independent approach for discovering viroids, a distinct class of free circular RNA subvir...
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.1117815109
更新日期:2012-03-06 00:00:00
abstract::Monoamines, including dopamine (DA), have been linked to aggression in various species. However, the precise role or roles served by the amine in aggression have been difficult to define because dopaminergic systems influence many behaviors, and all can be altered by changing the function of dopaminergic neurons. In 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.1303446110
更新日期:2013-04-09 00:00:00
abstract::The class of neurons within the visual cortex of normal adult cats that has the smallest receptive fields (less than or equal to 2.25 degrees2) and that responds only to low rates of stimulus motion (less than or equal to 50 degrees / sec) responds preferentially to lines oriented about either the horizontal axis (+/-...
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.74.3.1272
更新日期:1977-03-01 00:00:00
abstract::Immune function is an energetically costly physiological activity that potentially diverts calories away from less immediately essential life tasks. Among developing organisms, the allocation of energy toward immune function may lead to tradeoffs with physical growth, particularly in high-pathogen, low-resource enviro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1073/pnas.1717522115
更新日期:2018-04-24 00:00:00
abstract::The budding yeast Saccharomyces cerevisiae initiates polarized growth or budding once per cell cycle at a specific time of the cell cycle and at a specific location on the cell surface. Little is known about the molecular nature of the temporal and spatial regulatory mechanisms. It is also unclear what factors, if any...
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.182370299
更新日期:2002-09-17 00:00:00
abstract::Some realistic galaxy models have been found to support discrete unstable spiral modes. Here, through the study of the relevant physical mechanisms and an extensive numerical investigation of the properties of the dominant modes in a wide class of galactic equilibria, we show how spiral structures are excited with dif...
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.79.12.3908
更新日期:1982-06-01 00:00:00
abstract::The differentiation of skeletal myoblasts is characterized by permanent withdrawal from the cell cycle and fusion into multinucleated myotubes. Muscle cell survival is critically dependent on the ability of cells to respond to oxidative stress. Base excision repair (BER) is the main repair mechanism of oxidative DNA 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.0701743104
更新日期:2007-10-23 00:00:00
abstract::The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation 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.1601485113
更新日期:2016-08-02 00:00:00
abstract::The superficial gray layer of the superior colliculus contains a map that represents the visual field, whereas the underlying intermediate gray layer contains a vector map of the saccades that shift the direction of gaze. These two maps are aligned so that a particular region of the visual field is represented directl...
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.94.24.13299
更新日期:1997-11-25 00:00:00
abstract::During latent infection of humans with Mycobacterium tuberculosis, bacteria persist in the asymptomatic host within granulomas, organized collections of differentiated macrophages, and other immune cells. The mechanisms for persistence remain poorly understood, as is the metabolic and replicative state of the microbes...
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.002024599
更新日期:2002-03-19 00:00:00
abstract::Unlike tailed bacteriophages, which use a preformed tail for transporting their genomes into a host bacterium, the ssDNA bacteriophage ΦX174 is tailless. Using cryo-electron microscopy and time-resolved small-angle X-ray scattering, we show that lipopolysaccharides (LPS) form bilayers that interact with ΦX174 at an ic...
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.1716614114
更新日期:2017-12-26 00:00:00
abstract::The effect of 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent tumor promoter, on the synthesis of proteins in BALB/c 3T3 mouse fibroblasts has been studied. When [35S]methionine-labeled proteins synthesized after the addition of TPA were analyzed by one- or two-dimensional polyacrylamide gel electrophoresis, 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.79.6.1800
更新日期:1982-03-01 00:00:00
abstract::HU, the major DNA binding protein of Escherichia coli, exists in solution as a heterodimer composed of two highly homologous subunits: HU1, encoded by hupB; HU2, encoded by hupA. The purification of the HU protein from hupA- or hupB- bacteria showed that the hupB mutant strains synthesize normal amounts of the HU2 sub...
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.86.20.7691
更新日期:1989-10-01 00:00:00
abstract::The human beta-globin locus control region (LCR) consists of four erythroid-specific DNaseI hypersensitive sites (HSs) at the 5' end of the beta-globin cluster. The LCR functions over a long distance on chromosome 11 to regulate transcription and replication of the beta-globin genes. To determine whether the HSs funct...
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.94.9.4566
更新日期:1997-04-29 00:00:00
abstract::To probe the structure of the gamma heavy chain of membrane IgG and the mRNA and gene segments that encode it, we have analyzed cDNA clones derived from a gamma 1 membrane RNA of B lymphoma 2PK-3. The nucleotide sequence of the clones indicated that membrane gamma 1 chains bear a COOH-terminal 71-residue segment that ...
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.79.6.2008
更新日期:1982-03-01 00:00:00
abstract::High-resolution crystal structures of editing complexes of both duplex and single-stranded DNA bound to Escherichia coli DNA polymerase I large fragment (Klenow fragment) show four nucleotides of single-stranded DNA bound to the 3'-5' exonuclease active site and extending toward the polymerase active site. Melting 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.85.23.8924
更新日期:1988-12-01 00:00:00
abstract::Deinococcus radiodurans is among a small number of bacterial species that are extremely resistant to ionizing radiation, UV light, toxic chemicals, and desiccation. We measured proteome oxidation (i.e., protein carbonylation, PC) in D. radiodurans as well as in standard and evolved resistant strains of Escherichia col...
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.1009312107
更新日期:2010-08-10 00:00:00
abstract::The gene encoding the receptor for hyaluronan-mediated motility (RHAMM) is overexpressed in many human cancers. However, it is unclear whether RHAMM plays a causal role in tumor initiation or progression. Using somatic gene transfer in a mouse model of islet cell tumorigenesis, we demonstrate that RHAMM isoform B (RHA...
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.1114022108
更新日期:2011-10-04 00:00:00
abstract::Allozyme, morphological, and PCR-generated mtDNA markers were used to analyze hybrid parentage and introgression between the neighboringly sympatric crustaceans Daphnia galeata mendotae and Daphnia rosea. mtDNA analysis of D. galeata mendotae from 15 lakes and of D. rosea from 8 lakes revealed species-specific fragmen...
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.90.15.7079
更新日期:1993-08-01 00:00:00