Stochastic Resonance in Ion Channels Characterized by Information Theory

We identify a unifying measure for stochastic resonance (SR) in voltage dependent ion channels which comprises periodic (conventional), aperiodic and nonstationary SR. Within a simplest setting, the gating dynamics is governed by two-state conductance fluctuations, which switch at random time points between two values. The corresponding continuous time point process is analyzed by virtue of information theory. In pursuing this goal we evaluate for our dynamics the tau-information, the mutual information and the rate of information gain. As a main result we find an analytical formula for the rate of information gain that solely involves the probability of the two channel states and their noise averaged rates. For small voltage signals it simplifies to a handy expression. Our findings are applied to study SR in a potassium channel. We find that SR occurs only when the closed state is predominantly dwelled. Upon increasing the probability for the open channel state the application of an extra dose of noise monotonically deteriorates the rate of information gain, i.e., no SR behavior occurs.Comment: 10 pages, 2 figures, to appear in Phys. Rev.

Force and Motion Generation of Molecular Motors: A Generic Description

We review the properties of biological motor proteins which move along linear filaments that are polar and periodic. The physics of the operation of such motors can be described by simple stochastic models which are coupled to a chemical reaction. We analyze the essential features of force and motion generation and discuss the general properties of single motors in the framework of two-state models. Systems which contain large numbers of motors such as muscles and flagella motivate the study of many interacting motors within the framework of simple models. In this case, collective effects can lead to new types of behaviors such as dynamic instabilities of the steady states and oscillatory motion.Comment: 29 pages, 9 figure

Ion-beam excitation of liquid argon

The scintillation light of liquid argon has been recorded wavelength and time resolved with very good statistics in a wavelength interval ranging from 118 nm through 970 nm. Three different ion beams, protons, sulfur ions and gold ions, were used to excite liquid argon. Only minor differences were observed in the wavelength-spectra obtained with the different incident particles. Light emission in the wavelength range of the third excimer continuum was found to be strongly suppressed in the liquid phase. In time-resolved measurements, the time structure of the scintillation light can be directly attributed to wavelength in our studies, as no wavelength shifter has been used. These measurements confirm that the singlet-to-triplet intensity ratio in the second excimer continuum range is a useful parameter for particle discrimination, which can also be employed in wavelength-integrated measurements as long as the sensitivity of the detector system does not rise steeply for wavelengths longer than 190 nm. Using our values for the singlet-to-triplet ratio down to low energies deposited a discrimination threshold between incident protons and sulfur ions as low as ∼2.5 keV seems possible, which represents the principle limit for the discrimination of these two species in liquid argon

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Maladaptive consumption: Definition, theoretical framework, and research propositions

Maladaptive consumption represents potentially uncontrollable and self-and others-harming consumer choices to fulfill a desire for rewarding substances and behaviors. More recently, maladaptive consumption has emerged as a pivotal interest within consumer research, and a deliberation of current developments regarding consumers’ misuse of substances and their repetitive engagement in certain behaviors highlights its acute importance. After summarizing both long-standing and emerging types of maladaptive consumption, we review mounting evidence and provide a working definition and an integrative theoretical framework for understanding antecedents, types, explanations, and consequences of maladaptive consumption. Finally, we close with a limited identification of propositions and research themes that suggest avenues for future research. © 2021 the Association for Consumer Research. All rights reserved.12 month embargo; published online: 27 May 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Conformational Dynamics of the Ligand-Binding Domain of Inward Rectifier K Channels as Revealed by Molecular Dynamics Simulations: Toward an Understanding of Kir Channel Gating

Inward rectifier (Kir) potassium channels are characterized by two transmembrane helices per subunit, plus an intracellular C-terminal domain that controls channel gating in response to changes in concentration of various ligands. Based on the crystal structure of the tetrameric C-terminal domain of Kir3.1, it is possible to build a homology model of the ATP-binding C-terminal domain of Kir6.2. Molecular dynamics simulations have been used to probe the dynamics of Kir C-terminal domains and to explore the relationship between their dynamics and possible mechanisms of channel gating. Multiple simulations, each of 10 ns duration, have been performed for Kir3.1 (crystal structure) and Kir6.2 (homology model), in both their monomeric and tetrameric forms. The Kir6.2 simulations were performed with and without bound ATP. The results of the simulations reveal comparable conformational stability for the crystal structure and the homology model. There is some decrease in conformational flexibility when comparing the monomers with the tetramers, corresponding mainly to the subunit interfaces in the tetramer. The β-phosphate of ATP interacts with the side chain of K185 in the Kir6.2 model and simulations. The flexibility of the Kir6.2 tetramer is not changed greatly by the presence of bound ATP, other than in two loop regions. Principal components analysis of the simulated dynamics suggests loss of symmetry in both the Kir3.1 and Kir6.2 tetramers, consistent with “dimer-of-dimers” motion of subunits in C-terminal domains of the corresponding Kir channels. This is suggestive of a gating model in which a transition between exact tetrameric symmetry and dimer-of-dimers symmetry is associated with a change in transmembrane helix packing coupled to gating of the channel. Dimer-of-dimers motion of the C-terminal domain tetramer is also supported by coarse-grained (anisotropic network model) calculations. It is of interest that loss of exact rotational symmetry has also been suggested to play a role in gating in the bacterial Kir homolog, KirBac1.1, and in the nicotinic acetylcholine receptor channel