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Search Results: 1 - 10 of 20692 matches for " Qing Nie "
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A Critical Quantity for Noise Attenuation in Feedback Systems
Liming Wang,Jack Xin,Qing Nie
PLOS Computational Biology , 2010, DOI: 10.1371/journal.pcbi.1000764
Abstract: Feedback modules, which appear ubiquitously in biological regulations, are often subject to disturbances from the input, leading to fluctuations in the output. Thus, the question becomes how a feedback system can produce a faithful response with a noisy input. We employed multiple time scale analysis, Fluctuation Dissipation Theorem, linear stability, and numerical simulations to investigate a module with one positive feedback loop driven by an external stimulus, and we obtained a critical quantity in noise attenuation, termed as “signed activation time”. We then studied the signed activation time for a system of two positive feedback loops, a system of one positive feedback loop and one negative feedback loop, and six other existing biological models consisting of multiple components along with positive and negative feedback loops. An inverse relationship is found between the noise amplification rate and the signed activation time, defined as the difference between the deactivation and activation time scales of the noise-free system, normalized by the frequency of noises presented in the input. Thus, the combination of fast activation and slow deactivation provides the best noise attenuation, and it can be attained in a single positive feedback loop system. An additional positive feedback loop often leads to a marked decrease in activation time, decrease or slight increase of deactivation time and allows larger kinetic rate variations for slow deactivation and fast activation. On the other hand, a negative feedback loop may increase the activation and deactivation times. The negative relationship between the noise amplification rate and the signed activation time also holds for the six other biological models with multiple components and feedback loops. This principle may be applicable to other feedback systems.
Incorporating Existing Network Information into Gene Network Inference
Scott Christley, Qing Nie, Xiaohui Xie
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006799
Abstract: One methodology that has met success to infer gene networks from gene expression data is based upon ordinary differential equations (ODE). However new types of data continue to be produced, so it is worthwhile to investigate how to integrate these new data types into the inference procedure. One such data is physical interactions between transcription factors and the genes they regulate as measured by ChIP-chip or ChIP-seq experiments. These interactions can be incorporated into the gene network inference procedure as a priori network information. In this article, we extend the ODE methodology into a general optimization framework that incorporates existing network information in combination with regularization parameters that encourage network sparsity. We provide theoretical results proving convergence of the estimator for our method and show the corresponding probabilistic interpretation also converges. We demonstrate our method on simulated network data and show that existing network information improves performance, overcomes the lack of observations, and performs well even when some of the existing network information is incorrect. We further apply our method to the core regulatory network of embryonic stem cells utilizing predicted interactions from two studies as existing network information. We show that including the prior network information constructs a more closely representative regulatory network versus when no information is provided.
A reaction–diffusion mechanism influences cell lineage progression as a basis for formation, regeneration, and stability of intestinal crypts
Lei Zhang, Arthur D Lander, Qing Nie
BMC Systems Biology , 2012, DOI: 10.1186/1752-0509-6-93
Abstract: We present a mathematical model that contains Wnt and BMP, a cell lineage, and their feedback regulations to study formation, regeneration, and stability of multiple crypts. The computational explorations and linear stability analysis of the model suggest a reaction–diffusion mechanism, which exhibits a short-range activation of Wnt plus a long-range inhibition with modulation of BMP signals in a growing tissue of cell lineage, can account for spontaneous formation of multiple crypts with the spatial and temporal pattern observed in experiments. Through this mechanism, the model can recapitulate some distinctive and important experimental findings such as crypt regeneration and crypt multiplication. BMP is important in maintaining stability of crypts and loss of BMP usually leads to crypt multiplication with a fingering pattern.The study provides a mechanism for de novo formation of multiple intestinal crypts and demonstrates a synergetic role of Wnt and BMP in regeneration and stability of intestinal crypts. The proposed model presents a robust framework for studying spatial and temporal dynamics of cell lineages in growing tissues driven by multiple signaling molecules.The colonic crypt, a basic functional unit of the intestine, is made up of a single sheet of columnar epithelial cells, which form finger-like invaginations into the underlying connective tissue of lamina propria [1]. A human colon that consists of millions of crypts undergoes continual self-renewal and the intestinal epithelium is completely renewed within 3–5?days in humans [2]. Evidence has pointed to the location of the stem-cell population at the base of the crypt, within the stem-cell niche, formed by the stem cells themselves and mesenchymal cells that surround the crypt base [3]. Stem cells are thought to feed a spatial compartment above the crypt base where most cell proliferation occurs. This part of crypt is thought to house the transit-amplifying (TA) cells that may be committed to one o
Ultrasensitive Responses and Specificity in Cell Signaling
Seth Haney, Lee Bardwell, Qing Nie
BMC Systems Biology , 2010, DOI: 10.1186/1752-0509-4-119
Abstract: We studied the behavior of simple mathematical models of signaling networks composed of two interconnected pathways that share an intermediate component, asking if the two pathways in the network could exhibit both output specificity (preferentially activate their own output) and input fidelity (preferentially respond to their own input). Previous results with weakly-activated pathways indicated that neither mutual specificity nor mutual fidelity were obtainable in the absence of an insulating mechanism, such as cross-pathway inhibition, combinatorial signaling or scaffolding/compartmentalization. Here we found that mutual specificity is obtainable for hyperbolic or ultrasensitive pathways, even in the absence of an insulating mechanism. However, mutual fidelity is impossible at steady-state, even if pathways are hyperbolic or ultrasensitive. Nevertheless, ultrasensitivity does provide advantages in attaining specificity and fidelity to networks that contain an insulating mechanism. For networks featuring cross-pathway inhibition or combinatorial signaling, ultrasensitive activation can increase specificity in a limited way, and can only be utilized by one of the two pathways. In contrast, for networks featuring scaffolding/compartmentalization, ultrasensitive activation of both pathways can dramatically improve network specificity.There are constraints to obtaining performance objectives associated with signaling specificity; such constraints may have influenced the evolution of signal transduction networks. Notably, input fidelity (preferential response to an authentic input) is a more difficult objective to achieve than output specificity (preferential targeting to an authentic output). Indeed, mutual fidelity is impossible in the absence of an insulating mechanism, even if pathways are ultrasensitive. Ultrasensitivity does, however, significantly enhance the performance of several insulating mechanisms. In particular, the ultrasensitive activation of both pathwa
The Interplay between Wnt Mediated Expansion and Negative Regulation of Growth Promotes Robust Intestinal Crypt Structure and Homeostasis
Huijing Du?,Qing Nie,William R. Holmes
PLOS Computational Biology , 2015, DOI: 10.1371/journal.pcbi.1004285
Abstract: The epithelium of the small intestinal crypt, which has a vital role in protecting the underlying tissue from the harsh intestinal environment, is completely renewed every 4–5 days by a small pool of stem cells at the base of each crypt. How is this renewal controlled and homeostasis maintained, particularly given the rapid nature of this process? Here, based on the recent observations from in vitro “mini gut” studies, we use a hybrid stochastic model of the crypt to investigate how exogenous niche signaling (from Wnt and BMP) combines with auto-regulation to promote homeostasis. This model builds on the sub-cellular element method to account for the three-dimensional structure of the crypt, external regulation by Wnt and BMP, internal regulation by Notch signaling, as well as regulation by internally generated diffusible signals. Results show that Paneth cell derived Wnt signals, which have been observed experimentally to sustain crypts in cultured organs, have a dramatically different influence on niche dynamics than does mesenchyme derived Wnt. While this signaling can indeed act as a redundant backup to the exogenous gradient, it introduces a positive feedback that destabilizes the niche and causes its uncontrolled expansion. We find that in this setting, BMP has a critical role in constraining this expansion, consistent with observations that its removal leads to crypt fission. Further results also point to a new hypothesis for the role of Ephrin mediated motility of Paneth cells, specifically that it is required to constrain niche expansion and maintain the crypt’s spatial structure. Combined, these provide an alternative view of crypt homeostasis where the niche is in a constant state of expansion and the spatial structure of the crypt arises as a balance between this expansion and the action of various sources of negative regulation that hold it in check.
Nonsingular Surface-Quasi-Geostrophic Flow
Peter Constantin,Qing Nie,Norbert Schorghofer
Physics , 1998, DOI: 10.1016/S0375-9601(98)00108-X
Abstract: The dynamics of large eddies in the atmosphere and oceans is described by the surface quasi geostrophic equation, which is reminiscent of the Euler equations. Thermal fronts build up rapidly. Two different numerical methods combined with analytical criteria are used to show there are no singularities in finite time.
Effect of Salinity on the Growth Performance, Body Composition, Antioxidant Indexes of Perinereis aibuhitensis and Total Nitrogen in the Substrate  [PDF]
Fu Lv, Qing Nie, Yebing Yu, Fei Liu, Linlan Lv, Weihong Zhao
Agricultural Sciences (AS) , 2017, DOI: 10.4236/as.2017.811089
Abstract: In this study, the effects of different salinity levels (9, 12, 15, 18, 21, 24, 27, 30, and 33) on the growth performance, body composition, antioxidant indexes of Perinereis aibuhitensis (initial average mass, 20.4 ± 0.3 mg) and total nitrogen in the substrate were investigated. The survival rate, specific growth rate, feed coefficient, and protein efficiency ratio under different salinity levels were measured. The results showed that the survival rate of P. aibuhitensis at the salinity level of 9 was significantly lower than that of P. aibuhitensis at other salinity levels (P < 0.05). However, the survival rate of P. aibuhitensis at other salinity levels was not significant (P > 0.05). On the basis of quadratic polynomial fitting of the relationship between salinity levels and the specific growth rate, feed coefficient, and protein efficiency ratio, it was concluded that 25.36 - 25.9 is the most suitable salinity range for the growth performance of P. aibuhitensis. The main body composition (moisture, crude fat, crude protein, and ash content) was measured at different salinity levels. The results indicated that, with the increase in salinity, the moisture content of P. aibuhitensis decreased gradually; in contrast, the ash content increased gradually, as the salinity level increased. However, in the salinity range of 18 to 33, the difference in ash content was not significant (P > 0.05). Salinity had a significant influence on the crude protein content (P < 0.05), while it had no significant influence on crude body fat. Crude protein showed an increasing trend with the salinity increasing from 9 to 24, and decreased with the salinity increasing from 24 to 33. Antioxidant indexes such as superoxide dismutase, catalase, glutathione, and malondialdehyde (MDA) were analyzed, showing that in vivo MDA content was as low as the antioxidant activity at the salinity level of 24; this means low in vivo contents of active oxygen free radicals and excellent growth performance. This conclusion is consistent with that for other growth indexes. The total nitrogen content of the substrate in which the P. aibuhitensis specimens were cultured for 60 days was higher than the total nitrogen in the soil. With an increase in salinity, the total nitrogen content first decreased and then increased, and the lowest value was observed at the salinity level of about 24.
Expression and subcellular localization of a novel gene Bm-X of the silkworm, Bombyx mori  [PDF]
Zhengbing Lv, Yunlong Liu, Ying Chen, Bo Li, Lili Liu, Jian Chen, Zuoming Nie, Qing Sheng, Wei Yu, Yaozhou Zhang
American Journal of Molecular Biology (AJMB) , 2012, DOI: 10.4236/ajmb.2012.23023
Abstract: According to the large-scale sequencing of cDNA library from silkworm pupae, the cDNA of a novel gene with blank research background was identified and temporarily named Bm-X. The length of this cDNA is 778 bp. We obtained its ORF for further study by bioinformatics analysis. It is 444 bp and encodes 147 amino acid residues, with a predicted molecular weight (MW) of 16.4 kD and an isoelectric point (pI) of 3.69. In this study, we successfully constructed a recombinant plasmid pET-28a(+)-Bm-X and expressed it in Escherichia coli. We used the fusion protein rBm-X which purified by Niaffinity chromatography to produce polyclonal antibodies against Bm-X for Western blot analysis. The analysis revealed that Bm-X was expressed in the larval midgut, the epidermis and the silk gland. In addition, the subcellular localization analysis of silkworm ovary epithelial cells (BmN cells) showed that Bm-X protein was located both in cytoplasm and nucleus, and the signal was stronger in cytoplasm than in nucleus. Our findings indicate that Bm-X gene is a novel species-specificity gene and its expression product can be detected in tissues of the fifth silkworm instar larvae and BmN cells.
The ?675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis
Wei Nie, Bing Li, Qing-yu Xiu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034385
Abstract: Background A number of studies assessed the association of ?675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. Methods Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. Results Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008). Conclusions This meta-analysis suggested that the ?675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.
Modeling Robustness Tradeoffs in Yeast Cell Polarization Induced by Spatial Gradients
Ching-Shan Chou, Qing Nie, Tau-Mu Yi
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003103
Abstract: Cells localize (polarize) internal components to specific locations in response to external signals such as spatial gradients. For example, yeast cells form a mating projection toward the source of mating pheromone. There are specific challenges associated with cell polarization including amplification of shallow external gradients of ligand to produce steep internal gradients of protein components (e.g. localized distribution), response over a broad range of ligand concentrations, and tracking of moving signal sources. In this work, we investigated the tradeoffs among these performance objectives using a generic model that captures the basic spatial dynamics of polarization in yeast cells, which are small. We varied the positive feedback, cooperativity, and diffusion coefficients in the model to explore the nature of this tradeoff. Increasing the positive feedback gain resulted in better amplification, but also produced multiple steady-states and hysteresis that prevented the tracking of directional changes of the gradient. Feedforward/feedback coincidence detection in the positive feedback loop and multi-stage amplification both improved tracking with only a modest loss of amplification. Surprisingly, we found that introducing lateral surface diffusion increased the robustness of polarization and collapsed the multiple steady-states to a single steady-state at the cost of a reduction in polarization. Finally, in a more mechanistic model of yeast cell polarization, a surface diffusion coefficient between 0.01 and 0.001 μm2/s produced the best polarization performance, and this range is close to the measured value. The model also showed good gradient-sensitivity and dynamic range. This research is significant because it provides an in-depth analysis of the performance tradeoffs that confront biological systems that sense and respond to chemical spatial gradients, proposes strategies for balancing this tradeoff, highlights the critical role of lateral diffusion of proteins in the membrane on the robustness of polarization, and furnishes a framework for future spatial models of yeast cell polarization.
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