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Repeated small perturbation approach reveals transcriptomic steady states.

ABSTRACT: The study of biological systems dynamics requires elucidation of the transitions of steady states. A "small perturbation" approach can provide important information on the "steady state" of a biological system. In our experiments, small perturbations were generated by applying a series of repeating small doses of ultraviolet radiation to a human keratinocyte cell line, HaCaT. The biological response was assessed by monitoring the gene expression profiles using cDNA microarrays. Repeated small doses (10 J/m2) of ultraviolet B (UVB) exposure modulated the expression profiles of two groups of genes in opposite directions. The genes that were up-regulated have functions mainly associated with anti-proliferation/anti-mitogenesis/apoptosis, and the genes that were down-regulated were mainly related to proliferation/mitogenesis/anti-apoptosis. For both groups of genes, repetition of the small doses of UVB caused an immediate response followed by relaxation between successive small perturbations. This cyclic pattern was suppressed when large doses (233 or 582.5 J/m2) of UVB were applied. Our method and results contribute to a foundation for computational systems biology, which implicitly uses the concept of steady state.

SUBMITTER: Huang CL

PROVIDER: S-EPMC3240659 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Repeated small perturbation approach reveals transcriptomic steady states.

Huang Ching-Lung CL Shu Wun-Yi WY Tsai Min-Lung ML Chiang Chi-Shiun CS Chang Cheng-Wei CW Chang Chiu-Ting CT Hsu Ian C IC

PloS one 20111215 12

The study of biological systems dynamics requires elucidation of the transitions of steady states. A "small perturbation" approach can provide important information on the "steady state" of a biological system. In our experiments, small perturbations were generated by applying a series of repeating small doses of ultraviolet radiation to a human keratinocyte cell line, HaCaT. The biological response was assessed by monitoring the gene expression profiles using cDNA microarrays. Repeated small do ...[more]

PMID: 22195030

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Project description:The â??small perturbationâ?? approach is critical in studying the â??steady stateâ?? of a biological system. In our experiments, small perturbations were generated by applying a series of repeating intermittent small doses of ultraviolet radiation to a human keratinocyte cell line, HaCaT. The biological response was assessed by monitoring the gene expression profiles using a high reliability and high resolution cDNA microarray system. Following intermittent 10 J/m2 UVB small perturbations, two opposite classes of genes, down-regulated and up-regulated, exhibited an immediate response followed by relaxation between each small perturbation, but were prolonged down- or up-regulated without relaxation while larger doses (233 or 582.5 J/m2) of UVB were applied. A repeated cycle pattern of gene expression following small perturbations is an indication of the existence of steady states. This cycle pattern is suppressed when large perturbations are applied. We believe that this is a universal phenomenon. In our experiments, the functions of up-regulated genes were mainly associated with anti-proliferation, anti-mitogenesis, and apoptosis. On the other hand, down-regulated genes were mainly related to proliferation, mitogenesis, and anti-apoptosis. In conclusion, this study experimentally proves the concept of steady state at the transcription level and demonstrates the feasibility of using small perturbation approaches for investigating steady states. This study could also set a foundation of computational systems biology, which has implicitly used the concept of steady state. Keywords: time course Three UVB exposures are indicated by UV at time points of 0, 8 and 16 hours. T1, T2, T3, T4, T5, and T6 denote the sampling time points. T1, T3 and T5 are allocated 30 minutes after the corresponding UVB irradiation. T2, T4 and T6 are allocated 8 hours after each UVB irradiation. At each sampling time point, two samples (control and UV-irradiated) are collected. See supplementary file Loop_design.pdf for further explanation.

Project description:Gait is a large component and indicator of health. Many factors affect gait including age, disease, and even mood disorders. Few studies have looked at the influence of emotional states on gait. This study aimed to investigate the influence of emotional states on walking performance to understand whether an emotional state may be an important factor to consider when evaluating gait. Thirty-six young adults were recruited (23F, 13M) and performed a neutral baseline condition of walking which included six passes of walking across an 8m walkway (a total of 48m of walking). Participants then completed 6 pseudo-randomized emotional state induction conditions while immersive 360-degree videos were used to induce the following emotional conditions: happiness, excitement, sadness, fear, and anger. Participants viewed the emotion elicitation videos using a virtual reality head-mounted display (HMD), then rated their emotional state using self-assessment manikins and walked (without the HMD) over a pressure sensor walkway. One-way repeated measures ANOVA and pairwise comparisons were used to examine differences in gait parameters across the emotional conditions. Participants walked with significantly reduced step length and speed during the sadness condition compared to the other emotional conditions and the neutral condition. Furthermore, participants adjusted the timing of their walking during the sadness condition and walked with significantly increased step, stance, and swing times compared to other emotional conditions, but not the neutral condition. Step time was significantly reduced during the conditions of excitement and fear compared to the neutral condition. Emotions may impact variety of gait parameters involving pace and rhythm, however have little influence on gait variability and postural control. These results indicate that perhaps the emotions of sadness and excitement should be taken into account as potential confounds for future gait analysis.

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Repeated small perturbation approach reveals transcriptomic steady states.

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Repeated small perturbation approach reveals transcriptomic steady states.

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