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1.
Cognition ; 134: 155-64, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25460388

ABSTRACT

A prominent model suggests that individuals to the right of the political spectrum are more cognitively rigid and less tolerant of ambiguity than individuals to the left. On the basis of this model, we predicted that a psychological mechanism linked to the resolution of visual ambiguity--perceptual bias--would be linked to political attitude. Perceptual bias causes western individuals to favour a global interpretation when scrutinizing ambiguous hierarchical displays (e.g., alignment of trees) that can be perceived either in terms of their local elements (e.g., several trees) or in terms of their global structure (e.g., a forest). Using three tasks (based on Navon-like hierarchical figures or on the Ebbinghaus illusion), we demonstrate (1) that right-oriented Westerners present a stronger bias towards global perception than left-oriented Westerners and (2) that this stronger bias is linked to higher cognitive rigidity. This study establishes for the first time that political ideology, a high-level construct, is directly reflected in low-level perception. Right- and left-oriented individuals actually see the world differently.


Subject(s)
Attitude , Cognition/physiology , Illusions/physiology , Politics , Visual Perception/physiology , Adult , Female , Humans , Male , Middle Aged
2.
Biophys J ; 100(10): L56-8, 2011 May 18.
Article in English | MEDLINE | ID: mdl-21575565

ABSTRACT

Gene expression noise varies with genomic position and is a driving force in the evolution of chromosome organization. Nevertheless, position effects remain poorly characterized. Here, we present a systematic analysis of chromosomal position effects by characterizing single-cell gene expression from euchromatic positions spanning the length of a eukaryotic chromosome. We demonstrate that position affects gene expression by modulating the size of transcriptional bursts, rather than their frequency, and that the histone deacetylase Sir2 plays a role in this process across the chromosome.


Subject(s)
Chromosomal Position Effects/genetics , Chromosomes, Fungal/genetics , Gene Expression Regulation, Fungal , Saccharomyces cerevisiae/genetics , Silent Information Regulator Proteins, Saccharomyces cerevisiae/metabolism , Sirtuin 2/metabolism , Transcription, Genetic , Models, Genetic , Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics , Sirtuin 2/genetics , Stochastic Processes
3.
Syst Synth Biol ; 4(2): 105-16, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20805931

ABSTRACT

Recent studies indicate that intrinsic promoter-mediated gene expression noise can confer a selective advantage under acute environmental stress by providing beneficial phenotypic diversity within cell populations. To investigate how extrinsic gene expression noise impacts the fitness of cell populations under stress, we engineered two nearly isogenic budding yeast strains; one carrying a two-step regulatory cascade that allows for precise control of the noise transmitted from a transcriptional regulator to a downstream stress-inducing gene, and one carrying a network with low constant upstream noise. The fitness and gene expression of these strains were compared under acute and prolonged stress exposure. Using a phenomenological modeling approach, we predicted that increased noise should confer a fitness advantage under high stress conditions, but reciprocally reduce the resistance of the population to low stress. The model also predicted that extrinsic noise might serve as a basis for phenotypic plasticity whereby gene expression distributions are modulated in response to prolonged stress. Experimentally, we confirmed the predicted differential fitness advantage of extrinsic noise under acute stress, as well as the predicted modulation of gene expression under prolonged stress. However, contrary to model predictions, strains with low and high extrinsic noise showed very similar adaptive responses to prolonged stress. This suggests that while phenotypic heterogeneity generated by noise in regulatory signals can confer increased robustness to acute stress, it is not a requirement for the observed long-term phenotypic plasticity.

4.
FASEB J ; 18(15): 1937-9, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15456738

ABSTRACT

Duchenne muscular dystrophy (DMD) is a progressive and ultimately fatal skeletal muscle disease. Currently, the most effective therapy is the administration of a subclass of glucocorticoids, most notably deflazacort. Although deflazacort treatment can attenuate DMD progression, extend ambulation, and maintain muscle strength, the mechanism of its action remains unknown. Prior observations have shown that activation of a JNK1-mediated signal transduction cascade contributes to the progression of the DMD phenotype, in part by phosphorylation and inhibition of a calcineurin sensitive NF-ATc1 transcription factor. Here, we observed that deflazacort treatment restored myocyte viability in muscle cells with constitutive activation of JNK1 and in dystrophic mdx mice. However, deflazacort treatment did not alter JNK1 activity itself, but rather led to an increase in the activity of the calcineurin phosphatase and an up-regulation of NF-ATc1-dependent gene expression. The prophylactic effect of deflazacort treatment was associated with increased expression of NF-ATc1 target genes such as the dystrophin homologue utrophin. Moreover, the muscle sparing effects of deflazacort were completely abolished when used in conjunction with the calcineurin inhibitor cyclosporine. Collectively, these results show that deflazacort attenuates loss of dystrophic myofiber integrity by up-regulating the activity of the phosphatase calcineurin, which in turn negates JNK1 inhibition of NF-ATc1-mediated phosphorylation and nuclear exclusion of NF-ATc1.


Subject(s)
Calcineurin/metabolism , DNA-Binding Proteins/metabolism , Muscle Fibers, Skeletal/drug effects , Muscular Dystrophy, Duchenne/metabolism , Nuclear Proteins/metabolism , Pregnenediones/pharmacology , Transcription Factors/metabolism , Active Transport, Cell Nucleus , Animals , Cell Nucleus/metabolism , Enzyme Activation , Mice , Mice, Inbred mdx , Mitogen-Activated Protein Kinase 8/antagonists & inhibitors , Muscle Fibers, Skeletal/enzymology , Muscle Fibers, Skeletal/pathology , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/pathology , NFATC Transcription Factors , Pregnenediones/therapeutic use , Signal Transduction/drug effects , Transcriptional Activation , Utrophin/metabolism
5.
Proc Natl Acad Sci U S A ; 100(13): 7791-6, 2003 Jun 24.
Article in English | MEDLINE | ID: mdl-12808150

ABSTRACT

Utrophin levels have recently been shown to be more abundant in slow vs. fast muscles, but the nature of the molecular events underlying this difference remains to be fully elucidated. Here, we determined whether this difference is due to the expression of utrophin A or B, and examined whether transcriptional regulatory mechanisms are also involved. Immunofluorescence experiments revealed that slower fibers contain significantly more utrophin A in extrasynaptic regions as compared with fast fibers. Single-fiber RT-PCR analysis demonstrated that expression of utrophin A transcripts correlates with the oxidative capacity of muscle fibers, with cells expressing myosin heavy chain I and IIa demonstrating the highest levels. Functional muscle overload, which stimulates expression of a slower, more oxidative phenotype, induced a significant increase in utrophin A mRNA levels. Because calcineurin has been implicated in controlling this slower, high oxidative myofiber program, we examined expression of utrophin A transcripts in muscles having altered calcineurin activity. Calcineurin inhibition resulted in an 80% decrease in utrophin A mRNA levels. Conversely, muscles from transgenic mice expressing an active form of calcineurin displayed higher levels of utrophin A transcripts. Electrophoretic mobility shift and supershift assays revealed the presence of a nuclear factor of activated T cells (NFAT) binding site in the utrophin A promoter. Transfection and direct gene transfer studies showed that active forms of calcineurin or nuclear NFATc1 transactivate the utrophin A promoter. Together, these results indicate that expression of utrophin A is related to the oxidative capacity of muscle fibers, and implicate calcineurin and its effector NFAT in this mechanism.


Subject(s)
Calcineurin/metabolism , DNA-Binding Proteins/metabolism , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Nuclear Proteins , Oxygen/metabolism , RNA, Messenger/metabolism , Signal Transduction , Transcription Factors/metabolism , Animals , Blotting, Western , Cytoskeletal Proteins/biosynthesis , Cytoskeletal Proteins/genetics , Gene Transfer Techniques , Genes, Reporter , Immunoblotting , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Microscopy, Fluorescence , NFATC Transcription Factors , Phenotype , Promoter Regions, Genetic , Protein Isoforms , RNA/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Utrophin
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