The Utility of Paradoxical Components in Biological Circuits

Hart, Yuval; Alon, Uri

doi:10.1016/j.molcel.2013.01.004

Cited by 148 publications

(166 citation statements)

References 102 publications

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“…Similar biphasic filters have been found in numerous other systems (Hart and Alon, 2013;Kato et al, 2014;Nagel and Doupe, 2006); there they are proposed to support efficient coding (Atick and Redlich, 1990;Zhao and Zhaoping, 2011). Here, we add another aspect that makes biphasic filters advantageous: the two lobes correspond to two neuronal response features -tonic and phasic -and signal distinct song features -song amount and bout number.…”

Section: Linking Computations In the Auditory Pathway With Female Behmentioning

confidence: 54%

Connecting Neural Codes with Behavior in the Auditory System of Drosophila

Clemens¹,

Girardin²,

Coen³

et al. 2018

Neuron

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SummaryBrains are optimized for processing ethologically relevant sensory signals. However, few studies have characterized the neural coding mechanisms that underlie the transformation from natural sensory information to behavior. Here, we focus on acoustic communication in Drosophila melanogaster, and use computational modeling to link natural courtship song, neuronal codes, and female behavioral responses to song. We show that melanogaster females are sensitive to long timescale song structure (on the order of tens of seconds). From intracellular recordings, we generate models that recapitulate neural responses to acoustic stimuli. We link these neural codes with female behavior by generating model neural responses to natural courtship song. Using a simple decoder, we predict female behavioral responses to the same song stimuli with high accuracy. Our modeling approach reveals how long timescale song features are represented by the Drosophila brain, and how neural representations can be decoded to generate behavioral selectivity for acoustic communication signals.

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Section: Linking Computations In the Auditory Pathway With Female Behmentioning

confidence: 54%

Connecting Neural Codes with Behavior in the Auditory System of Drosophila

Clemens¹,

Girardin²,

Coen³

et al. 2018

Neuron

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“…Rather, they operate in a large number of biological contexts, spatial, and temporal scales and functional states exemplified by protein‐specific properties such as reaction mechanisms, substrate/ motif binding and complex formation. In addition, properties of protein networks such as information processing, noise, adaptability, robustness, and even seemingly paradoxical arrangement of components and functions, such as enzyme promiscuity 19, 20, 21, 22, 23, 24, 25, 26. Moreover, a protein can exist with different variant sequences due to splicing or mutations, and be subject to different PTMs at different sites, resulting in a vast number of theoretical combination of PTMs, known as “mod‐forms”, see for example the histone‐code 18.…”

Section: Introductionmentioning

confidence: 99%

Applications of targeted proteomics in systems biology and translational medicine

et al. 2015

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Biological systems are composed of numerous components of which proteins are of particularly high functional significance. Network models are useful abstractions for studying these components in context. Network representations display molecules as nodes and their interactions as edges. Because they are difficult to directly measure, functional edges are frequently inferred from suitably structured datasets consisting of the accurate and consistent quantification of network nodes under a multitude of perturbed conditions. For the precise quantification of a finite list of proteins across a wide range of samples, targeted proteomics exemplified by selected/multiple reaction monitoring (SRM, MRM) mass spectrometry has proven useful and has been applied to a variety of questions in systems biology and clinical studies. Here, we survey the literature of studies using SRM‐MS in systems biology and clinical proteomics. Systems biology studies frequently examine fundamental questions in network biology, whereas clinical studies frequently focus on biomarker discovery and validation in a variety of diseases including cardiovascular disease and cancer. Targeted proteomics promises to advance our understanding of biological networks and the phenotypic significance of specific network states and to advance biomarkers into clinical use.

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“…A biexponential function can be used to fit these curves, wherein one exponent corresponds to the timescale of activation and one corresponds to the timescale of inhibition. Hart and coworkers (12,13) identified that network motifs with bifunctional enzymes, which control activation and inhibition, can be thought of as paradoxical, because the same stimulus seems to control the activation and the inhibition in response to the same stimulus. This circuit is a special case of the incoherent feedforward loop (13).…”

mentioning

confidence: 99%

“…Hart and coworkers (12,13) identified that network motifs with bifunctional enzymes, which control activation and inhibition, can be thought of as paradoxical, because the same stimulus seems to control the activation and the inhibition in response to the same stimulus. This circuit is a special case of the incoherent feedforward loop (13). Paradoxical signaling has been identified in different contexts; examples include cellular homeostasis, cell population control, and actin dynamics through Arp2/3 and Arpin (12)(13)(14)(15).…”

mentioning

confidence: 99%

Paradoxical signaling regulates structural plasticity in dendritic spines

Rangamani

Levy

Khan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Transient spine enlargement (3-to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.CaMKII | dendritic spine | actin

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The Utility of Paradoxical Components in Biological Circuits

Cited by 148 publications

References 102 publications

Connecting Neural Codes with Behavior in the Auditory System of Drosophila

Connecting Neural Codes with Behavior in the Auditory System of Drosophila

Applications of targeted proteomics in systems biology and translational medicine

Paradoxical signaling regulates structural plasticity in dendritic spines

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