1,406 research outputs found

    Interlinked dual-time feedback loops can enhance robustness to stochasticity and persistence of memory.

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    Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular Ca2+ release. Recent studies with simplified models have identified two advantages of coupling fast and slow feedback loops. This dual-time structure enables a fast response while enhancing resistances of responses and bistability to stimulus noise. We now find that (1) the dual-time structure similarly confers resistance to internal noise due to molecule number fluctuations, and (2) model variants with altered coupling, which better represent some specific biochemical systems, share all the above advantages. We also develop a similar bistable model with coupling of a fast autoactivation loop to a slow loop. This model\u27s topology was suggested by positive feedback proposed to play a role in long-term synaptic potentiation (LTP). The advantages of fast response and noise resistance are also present in this autoactivation model. Empirically, LTP develops resistance to reversal over approximately 1h . The model suggests this resistance may result from increased amounts of synaptic kinases involved in positive feedback

    Mathematical Modeling of Gene Networks

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    Molecular mechanisms underlying a cellular analog of operant reward learning.

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    Operant conditioning is a ubiquitous but mechanistically poorly understood form of associative learning in which an animal learns the consequences of its behavior. Using a single-cell analog of operant conditioning in neuron B51 of Aplysia, we examined second-messenger pathways engaged by activity and reward and how they may provide a biochemical association underlying operant learning. Conditioning was blocked by Rp-cAMP, a peptide inhibitor of PKA, a PKC inhibitor, and by expressing a dominant-negative isoform of Ca2+-dependent PKC (apl-I). Thus, both PKA and PKC were necessary for operant conditioning. Injection of cAMP into B51 mimicked the effects of operant conditioning. Activation of PKC also mimicked conditioning but was dependent on both cAMP and PKA, suggesting that PKC acted at some point upstream of PKA activation. Our results demonstrate how these molecules can interact to mediate operant conditioning in an individual neuron important for the expression of the conditioned behavior

    Draft Genome Sequence of the Anaerobic, Nitrate-Dependent, Fe(II)-Oxidizing Bacterium \u3ci\u3ePseudogulbenkiania ferrooxidans\u3c/i\u3e Strain 2002

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    Pseudogulbenkiania ferrooxidans strain 2002 was isolated as a lithoautotrophic, Fe(II)-oxidizing, nitrate-reducing bacterium. Phylogenetically, it is in a clade within the family Neisseriaceae in the order Nessieriales of the class Betaproteobacteria. It is anticipated that comparative genomic analysis of this strain with other nitrate-dependent, Fe(II)-oxidizing bacteria will aid in the elucidation of the genetics and biochemistry underlying this critically important geochemical metabolism

    Going beyond richness: Modelling the BEF relationship using species identity, evenness, richness and species interactions via the DImodels R package, and a comparison with traditional approaches

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    BEF studies aim at understanding how ecosystems respond to a gradient of species diversity. Diversity-Interactions models are suitable for analysing the BEF relationship. These models relate an ecosystem function response of a community to the identity of the species in the community, their evenness (proportions) and interactions. The no. of species in the community (richness) is also implicitly modelled through this approach. It is common in BEF studies to model an ecosystem function as a function of richness; while this can uncover trends in the BEF relationship, by definition, species diversity is much broader than richness alone, and important patterns in the BEF relationship may remain hidden. We compare DI models to traditional modelling approaches to highlight the advantages of using a multi-dimensional definition of species diversity. DI models can capture variation due to species identities, species proportions and species interactions, in addition to richness effects. We also introduce the DImodels R package for implementing DI models. Through worked examples, we show that using DI models can lead to considerably improved model fit over other methods. Collapsing the multiple dimensions of species diversity to a single dimension (such as richness) can result in valuable ecological information being lost. Predicting from a DI model is not limited to the study design points, the model can extrapolate to predict for any species composition and proportions. Overall, DI models lead to enhanced inference compared to other approaches. Expressing the BEF relationship as a function of richness alone can be useful to capture overall trends, however, there are multiple ways to quantify the species diversity of a community. DI modelling provides a framework to test the multiple aspects of species diversity and facilitates uncovering a deeper ecological understanding of the BEF relationship
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