4,324 research outputs found
Telling time with an intrinsically noisy clock
Intracellular transmission of information via chemical and transcriptional
networks is thwarted by a physical limitation: the finite copy number of the
constituent chemical species introduces unavoidable intrinsic noise. Here we
provide a method for solving for the complete probabilistic description of
intrinsically noisy oscillatory driving. We derive and numerically verify a
number of simple scaling laws. Unlike in the case of measuring a static
quantity, response to an oscillatory driving can exhibit a resonant frequency
which maximizes information transmission. Further, we show that the optimal
regulatory design is dependent on the biophysical constraints (i.e., the
allowed copy number and response time). The resulting phase diagram illustrates
under what conditions threshold regulation outperforms linear regulation.Comment: 10 pages, 5 figure
Electron transport through multilevel quantum dot
Quantum transport properties through some multilevel quantum dots sandwiched
between two metallic contacts are investigated by the use of Green's function
technique. Here we do parametric calculations, based on the tight-binding
model, to study the transport properties through such bridge systems. The
electron transport properties are significantly influenced by (a) number of
quantized energy levels in the dots, (b) dot-to-electrode coupling strength,
(c) location of the equilibrium Fermi energy and (d) surface disorder. In
the limit of weak-coupling, the conductance () shows sharp resonant peaks
associated with the quantized energy levels in the dots, while, they get
substantial broadening in the strong-coupling limit. The behavior of the
electron transfer through these systems becomes much more clearly visible from
our study of current-voltage (-) characteristics. In this context we also
describe the noise power of current fluctuations () and determine the Fano
factor () which provides an important information about the electron
correlation among the charge carriers. Finally, we explore a novel transport
phenomenon by studying the surface disorder effect in which the current
amplitude increases with the increase of the surface disorder strength in the
strong disorder regime, while, the amplitude decreases in the limit of weak
disorder. Such an anomalous behavior is completely opposite to that of bulk
disordered system where the current amplitude always decreases with the
disorder strength. It is also observed that the current amplitude strongly
depends on the system size which reveals the finite quantum size effect.Comment: 12 pages, 7 figure
NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II
Incontinentia Pigmenti (IP) is a rare X-linked disease characterized by early male lethality and multiple abnormalities in heterozygous females. IP is caused by NF-κB essential modulator (NEMO) mutations. The current mechanistic model suggests that NEMO functions as a crucial component mediating the recruitment of the IκB-kinase (IKK) complex to tumor necrosis factor receptor 1 (TNF-R1), thus allowing activation of the pro-survival NF-κB response. However, recent studies have suggested that gene activation and cell death inhibition are two independent activities of NEMO. Here we describe that cells expressing the IP-associated NEMO-A323P mutant had completely abrogated TNF-induced NF-κB activation, but retained partial antiapoptotic activity and exhibited high sensitivity to death by necroptosis. We found that robust caspase activation in NEMO-deficient cells is concomitant with RIPK3 recruitment to the apoptosis-mediating complex. In contrast, cells expressing the ubiquitin-binding mutant NEMO-A323P did not recruit RIPK3 to complex II, an event that prevented caspase activation. Hence NEMO, independently from NF-κB activation, represents per se a key component in the structural and functional dynamics of the different TNF-R1-induced complexes. Alteration of this process may result in differing cellular outcomes and, consequently, also pathological effects in IP patients with different NEMO mutations
A stochastic spectral analysis of transcriptional regulatory cascades
The past decade has seen great advances in our understanding of the role of
noise in gene regulation and the physical limits to signaling in biological
networks. Here we introduce the spectral method for computation of the joint
probability distribution over all species in a biological network. The spectral
method exploits the natural eigenfunctions of the master equation of
birth-death processes to solve for the joint distribution of modules within the
network, which then inform each other and facilitate calculation of the entire
joint distribution. We illustrate the method on a ubiquitous case in nature:
linear regulatory cascades. The efficiency of the method makes possible
numerical optimization of the input and regulatory parameters, revealing design
properties of, e.g., the most informative cascades. We find, for threshold
regulation, that a cascade of strong regulations converts a unimodal input to a
bimodal output, that multimodal inputs are no more informative than bimodal
inputs, and that a chain of up-regulations outperforms a chain of
down-regulations. We anticipate that this numerical approach may be useful for
modeling noise in a variety of small network topologies in biology
Ubiquitin ligases and beyond
First paragraph (this article has no abstract): In a review published in 2004 [1] and that still repays reading today, Cecile Pickart traced the evolution of research on ubiquitination from its origins in the proteasomal degradation of proteins through the revelation that it has a central role in cell cycle regulation and the recognition of regulatory roles for ubiquitin in intracellular membrane transport, cell signalling, transcription, translation, and DNA repair
Onto better TRAILs for cancer treatment
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. By cross-linking TRAIL-Receptor (TRAIL-R) 1 or TRAIL-R2, also known as death receptors 4 and 5 (DR4 and DR5), TRAIL has the capability to induce apoptosis in a wide variety of tumor cells while sparing vital normal cells. The discovery of this unique property among TNF superfamily members laid the foundation for testing the clinical potential of TRAIL-R-targeting therapies in the cancer clinic. To date, two of these therapeutic strategies have been tested clinically: (i) recombinant human TRAIL and (ii) antibodies directed against TRAIL-R1 or TRAIL-R2. Unfortunately, however, these TRAIL-R agonists have basically failed as most human tumors are resistant to apoptosis induction by them. It recently emerged that this is largely due to the poor agonistic activity of these agents. Consequently, novel TRAIL-R-targeting agents with increased bioactivity are currently being developed with the aim of rendering TRAIL-based therapies more active. This review summarizes these second-generation novel formulations of TRAIL and other TRAIL-R agonists, which exhibit enhanced cytotoxic capacity toward cancer cells, thereby providing the potential of being more effective when applied clinically than first-generation TRAIL-R agonists
Entanglement and Tensor Product Decomposition for Two Fermions
The problem of the choice of tensor product decomposition in a system of two
fermions with the help of Bogoliubov transformations of creation and
annihilation operators is discussed. The set of physical states of the
composite system is restricted by the superselection rule forbidding the
superposition of fermions and bosons. It is shown that the Wootters concurrence
is not proper entanglement measure in this case. The explicit formula for the
entanglement of formation is found and its dependence on tensor product
decompositions of the Hilbert space is discussed. It is shown that the set of
separable states is narrower than in two-qubit case. Moreover, there exist
states which are separable with respect to all tensor product decompositions of
the Hilbert space.Comment: 8pp, published versio
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