Molecular Motors Interacting with Their Own Tracks

Dynamics of molecular motors that move along linear lattices and interact with them via reversible destruction of specific lattice bonds is investigated theoretically by analyzing exactly solvable discrete-state ``burnt-bridge'' models. Molecular motors are viewed as diffusing particles that can asymmetrically break or rebuild periodically distributed weak links when passing over them. Our explicit calculations of dynamic properties show that coupling the transport of the unbiased molecular motor with the bridge-burning mechanism leads to a directed motion that lowers fluctuations and produces a dynamic transition in the limit of low concentration of weak links. Interaction between the backward biased molecular motor and the bridge-burning mechanism yields a complex dynamic behavior. For the reversible dissociation the backward motion of the molecular motor is slowed down. There is a change in the direction of the molecular motor's motion for some range of parameters. The molecular motor also experiences non-monotonic fluctuations due to the action of two opposing mechanisms: the reduced activity after the burned sites and locking of large fluctuations. Large spatial fluctuations are observed when two mechanisms are comparable. The properties of the molecular motor are different for the irreversible burning of bridges where the velocity and fluctuations are suppressed for some concentration range, and the dynamic transition is also observed. Dynamics of the system is discussed in terms of the effective driving forces and transitions between different diffusional regimes

dimer paramagnetic centers in lead germanate crystals doped with iron and halogen (Cl-, Br-, F-) ions

The dimer complexes Fe3+-Cl-, Fe3+-Br-, and Fe3+-O2- in ferroelectric lead germanate crystals doped with iron and annealed in chlorine-, bromine-, and fluorine-containing atmospheres have been studied using the electron paramagnetic resonance method. These complexes are formed by Fe3+ ions in the trigonal position of lead and their associated anions located in the interstitial channel of the structure. The positions of the charge-compensating anions in the channel have been discussed based on the analysis of the parameters of the spin Hamiltonian and their temperature dependence. © 2013 Pleiades Publishing, Ltd

Electron paramagnetic resonance of Gd3+ ions in Ca1-x-yYxGdyF2+x+y crystals

Electron paramagnetic resonance of Ca1-x-yYxGdyF2+x+y single crystals has revealed spectra that are not typical of gadolinium-doped CaF2 crystals. These spectra have a nearly tetragonal symmetry and are most probably caused by Gd3+ ions localized in yttrium clusters. Weak spectra of tetragonal Gd3+ centers, whose parameters are close to those of a cubic gadolinium center caused by an isolated Gd3+ ion, have been also detected. These centers are attributed to isolated Gd3+ ions localized near octahedral rare-earth clusters or their associations. © 2013 Pleiades Publishing, Ltd

Specific features of the electron paramagnetic resonance spectrum in the vicinity of the convergence of the transitions of gadolinium centers in Pb5(Ge1 - xSix)3O11

An anomalous electron paramagnetic resonance spectrum of the transitions -1/2 ↔ +1/2 of four Gd3+-Si dimer clusters in the Pb5(Ge1 - xSix)3O11 crystals doped with gadolinium has been found in the vicinity of the orientation of the magnetic field along the optic axis of the crystal. It has been assumed that this spectrum is caused by rapid transitions between the spin packets of the initial resonances due to the crossrelaxation. A computer simulation of the spectrum has been carried out. The results obtained adequately describe the experiment. © 2013 Pleiades Publishing, Ltd

Tonic TCR Signaling Inversely Regulates the Basal Metabolism of CD4

The contribution of self-peptide-MHC signaling in CD

Thermodynamics of Electrolytes on Anisotropic Lattices

The phase behavior of ionic fluids on simple cubic and tetragonal (anisotropic) lattices has been studied by grand canonical Monte Carlo simulations. Systems with both the true lattice Coulombic potential and continuous-space $1/r$ electrostatic interactions have been investigated. At all degrees of anisotropy, only coexistence between a disordered low-density phase and an ordered high-density phase with the structure similar to ionic crystal was found, in contrast to recent theoretical predictions. Tricritical parameters were determined to be monotonously increasing functions of anisotropy parameters which is consistent with theoretical calculations based on the Debye-H\"uckel approach. At large anisotropies a two-dimensional-like behavior is observed, from which we estimated the dimensionless tricritical temperature and density for the two-dimensional square lattice electrolyte to be $T^*_{tri}=0.14$ and $\rho^*_{tri} = 0.70$.Comment: submitted to PR

Cell-intrinsic lysosomal lipolysis is essential for macrophage alternative activation

Alternative (M2) macrophage activation driven through interleukin 4 receptor α (IL-4Rα) is important for immunity to parasites, wound healing, the prevention of atherosclerosis and metabolic homeostasis. M2 polarization is dependent on fatty acid oxidation (FAO), but the source of fatty acids to support this metabolic program has not been clear. We show that the uptake of triacylglycerol substrates via CD36 and their subsequent lipolysis by lysosomal acid lipase (LAL) was important for the engagement of elevated oxidative phosphorylation (OXPHOS), enhanced spare respiratory capacity (SRC), prolonged survival and expression of genes that together define M2 activation. Inhibition of lipolysis suppressed M2 activation during infection with a parasitic helminth, and blocked protective responses against this pathogen. Our findings delineate a critical role for cell-intrinsic lysosomal lipolysis in M2 activation

A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules

Positive feedback plays a key role in the ability of signaling molecules to form highly localized clusters in the membrane or cytosol of cells. Such clustering can occur in the absence of localizing mechanisms such as pre-existing spatial cues, diffusional barriers, or molecular cross-linking. What prevents positive feedback from amplifying inevitable biological noise when an un-clustered “off” state is desired? And, what limits the spread of clusters when an “on” state is desired? Here, we show that a minimal positive feedback circuit provides the general principle for both suppressing and amplifying noise: below a critical density of signaling molecules, clustering switches off; above this threshold, highly localized clusters are recurrently generated. Clustering occurs only in the stochastic regime, suggesting that finite sizes of molecular populations cannot be ignored in signal transduction networks. The emergence of a dominant cluster for finite numbers of molecules is partly a phenomenon of random sampling, analogous to the fixation or loss of neutral mutations in finite populations. We refer to our model as the “neutral drift polarity model.” Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un-clustered states. The intrinsic ability of positive feedback both to create and suppress clustering is a general mechanism that could operate within diverse biological networks to create dynamic spatial organization

Mathematical models for immunology:current state of the art and future research directions

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years