Robust Control of PEP Formation Rate in the Carbon Fixation Pathway of C4 Plants by a Bi-functional Enzyme

<p>Abstract</p> <p>Background</p> <p>C₄plants such as corn and sugarcane assimilate atmospheric CO₂ into biomass by means of the C₄carbon fixation pathway. We asked how PEP formation rate, a key step in the carbon fixation pathway, might work at a precise rate, regulated by light, despite fluctuations in substrate and enzyme levels constituting and regulating this process.</p> <p>Results</p> <p>We present a putative mechanism for robustness in C₄carbon fixation, involving a key enzyme in the pathway, pyruvate orthophosphate dikinase (PPDK), which is regulated by a bifunctional enzyme, Regulatory Protein (RP). The robust mechanism is based on avidity of the bifunctional enzyme RP to its multimeric substrate PPDK, and on a product-inhibition feedback loop that couples the system output to the activity of the bifunctional regulator. The model provides an explanation for several unusual biochemical characteristics of the system and predicts that the system's output, phosphoenolpyruvate (PEP) formation rate, is insensitive to fluctuations in enzyme levels (PPDK and RP), substrate levels (ATP and pyruvate) and the catalytic rate of PPDK, while remaining sensitive to the system's input (light levels).</p> <p>Conclusions</p> <p>The presented PPDK mechanism is a new way to achieve robustness using product inhibition as a feedback loop on a bifunctional regulatory enzyme. This mechanism exhibits robustness to protein and metabolite levels as well as to catalytic rate changes. At the same time, the output of the system remains tuned to input levels.</p

Plasticity of the cis-Regulatory Input Function of a Gene

The transcription rate of a gene is often controlled by several regulators that bind specific sites in the gene's cis-regulatory region. The combined effect of these regulators is described by a cis-regulatory input function. What determines the form of an input function, and how variable is it with respect to mutations? To address this, we employ the well-characterized lac operon of Escherichia coli, which has an elaborate input function, intermediate between Boolean AND-gate and OR-gate logic. We mapped in detail the input function of 12 variants of the lac promoter, each with different point mutations in the regulator binding sites, by means of accurate expression measurements from living cells. We find that even a few mutations can significantly change the input function, resulting in functions that resemble Pure AND gates, OR gates, or single-input switches. Other types of gates were not found. The variant input functions can be described in a unified manner by a mathematical model. The model also lets us predict which functions cannot be reached by point mutations. The input function that we studied thus appears to be plastic, in the sense that many of the mutations do not ruin the regulation completely but rather result in new ways to integrate the inputs

Paradoxical Signaling by a Secreted Molecule Leads to Homeostasis of Cell Levels

SummaryA widespread feature of extracellular signaling in cell circuits is paradoxical pleiotropy: the same secreted signaling molecule can induce opposite effects in the responding cells. For example, the cytokine IL-2 can promote proliferation and death of T cells. The role of such paradoxical signaling remains unclear. To address this, we studied CD4+ T cell expansion in culture. We found that cells with a 30-fold difference in initial concentrations reached a homeostatic concentration nearly independent of initial cell levels. Below an initial threshold, cell density decayed to extinction (OFF-state). We show that these dynamics relate to the paradoxical effect of IL-2, which increases the proliferation rate cooperatively and the death rate linearly. Mathematical modeling explained the observed cell and cytokine dynamics and predicted conditions that shifted cell fate from homeostasis to the OFF-state. We suggest that paradoxical signaling provides cell circuits with specific dynamical features that are robust to environmental perturbations

Black hole polarization and new entropy bounds

Zaslavskii has suggested how to tighten Bekenstein's bound on entropy when the object is electrically charged. Recently Hod has provided a second tighter version of the bound applicable when the object is rotating. Here we derive Zaslavskii's optimized bound by considering the accretion of an ordinary charged object by a black hole. The force originating from the polarization of the black hole by a nearby charge is central to the derivation of the bound from the generalized second law. We also conjecture an entropy bound for charged rotating objects, a synthesis of Zaslavskii's and Hod's. On the basis of the no hair principle for black holes, we show that this last bound cannot be tightened further in a generic way by knowledge of ``global'' conserved charges, e.g., baryon number, which may be borne by the object.Comment: 21 pages, RevTex, Regularization of potential made clearer. Error in energy of the particle corrected with no consequence for final conclusions. New references adde

Causal Entropy Bound for Non-Singular Cosmologies

The conditions for validity of the Causal Entropy Bound (CEB) are verified in the context of non-singular cosmologies with classical sources. It is shown that they are the same conditions that were previously found to guarantee validity of the CEB: the energy density of each dynamical component of the cosmic fluid needs to be sub-Planckian and not too negative, and its equation of state needs to be causal. In the examples we consider, the CEB is able to discriminate cosmologies which suffer from potential physical problems more reliably than the energy conditions appearing in singularity theorems.Comment: 16 pages, no figures, acknowledgments adde

No hair for spherical black holes: charged and nonminimally coupled scalar field with self--interaction

We prove three theorems in general relativity which rule out classical scalar hair of static, spherically symmetric, possibly electrically charged black holes. We first generalize Bekenstein's no--hair theorem for a multiplet of minimally coupled real scalar fields with not necessarily quadratic action to the case of a charged black hole. We then use a conformal map of the geometry to convert the problem of a charged (or neutral) black hole with hair in the form of a neutral self--interacting scalar field nonminimally coupled to gravity to the preceding problem, thus establishing a no--hair theorem for the cases with nonminimal coupling parameter $\xi<0$ or $\xi\geq {1\over 2}$. The proof also makes use of a causality requirement on the field configuration. Finally, from the required behavior of the fields at the horizon and infinity we exclude hair of a charged black hole in the form of a charged self--interacting scalar field nonminimally coupled to gravity for any $\xi$.Comment: 30 pages, RevTeX. Sec.IV corrected, simplified and shortened. Corrections to Sec.IIA between Eqs. 2.7 and Eq.2.1. First two paragraphs of Sec. VC new. To appear Phys. Rev. D, Oct. 15, 199