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At least 1,063 records · Page 59

Phosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney: IMPLICATIONS FOR AMP KINASE

Mammalian cytochrome c (Cytc) plays a key role in cellular life and death decisions, functioning as an electron carrier in the electron transport chain and as a trigger of apoptosis when released from the mitochondria. However, its regulation is not well understood. We show that the major fraction of Cytc isolated from kidneys is phosphorylated on Thr28, leading to a partial inhibition of respiration in the reaction with cytochrome c oxidase. To further study the effect of Cytc phosphorylation in vitro, we generated T28E phosphomimetic Cytc, revealing superior behavior regarding protein stability and its ability to degrade reactive oxygen species compared with wild-type unphosphorylated Cytc. Introduction of T28E phosphomimetic Cytc into Cytc knock-out cells shows that intact cell respiration, mitochondrial membrane potential (ΔΨm), and ROS levels are reduced compared with wild type. As we show by high resolution crystallography of wild-type and T28E Cytc in combination with molecular dynamics simulations, Thr28 is located at a central position near the heme crevice, the most flexible epitope of the protein apart from the N and C termini. Finally, in silico prediction and our experimental data suggest that AMP kinase, which phosphorylates Cytc on Thr28 in vitro and colocalizes with Cytc to the mitochondrial intermembrane space in the kidney, is the most likely candidate to phosphorylate Thr28 in vivo. We conclude that Cytc phosphorylation is mediated in a tissue-specific manner and leads to regulation of electron transport chain flux via “controlled respiration,” preventing ΔΨm hyperpolarization, a known cause of ROS and trigger of apoptosis.

59 BASIC BIOLOGICAL SCIENCES↗

Supporting Technology for Chain of Custody of Nuclear Weapons and Materials throughout the Dismantlement and Disposition Processes

The ratification and ongoing implementation of the New START Treaty have been widely regarded as noteworthy global security achievements for both the Obama Administration and the Putin (formerly Medvedev) regime. But deeper cuts that move beyond the United States and Russia to engage the P-5 and other nuclear weapons possessor states are envisioned under future arms control regimes, and are indeed required for the P-5 in accordance with their Article VI disarmament obligations in the Nuclear Non-Proliferation Treaty. Future verification needs will include monitoring the cessation of production of new fissile material for weapons, monitoring storage of warhead components and fissile materials and verifying dismantlement of warheads, pits, secondary stages, and other materials. A fundamental challenge to implementing a nuclear disarmament regime is the ability to thwart unauthorized material diversion throughout the dismantlement and disposition process through strong chain of custody implementation. Verifying the declared presence, or absence, of nuclear materials and weapons components throughout the dismantlement and disposition lifecycle is a critical aspect of the disarmament process. From both the diplomatic and technical perspectives, verification under these future arms control regimes will require new solutions. Since any acceptable verification technology must protect sensitive design information and attributes to prevent the release of classified or other proliferation-sensitive information, non-nuclear non-sensitive modalities may provide significant new verification tools which do not require the use of additional information barriers. Alternative verification technologies based upon electromagnetic and acoustics could potentially play an important role in fulfilling the challenging requirements of future verification regimes. For example, researchers at the Pacific Northwest National Laboratory (PNNL) have demonstrated that low frequency electromagnetic signatures of sealed metallic containers can be used to rapidly confirm the presence of specific components on a yes/no basis without revealing classified information. PNNL researchers have also used ultrasonic measurements to obtain images of material microstructures which may be used as templates or unique identifiers of treaty-limited items. Such alternative technologies are suitable for application in various stages of weapons dismantlement and often include the advantage of an inherent information barrier due to the inability to extract classified weapon design information from the collected data. As a result, these types of technologies complement radiation-based verification methods for arms control. This article presents an overview of several alternative verification technologies that are suitable for supporting a future, broader and more intrusive arms control regime that spans the nuclear weapons disarmament lifecycle. The general capabilities and limitations of each verification modality are discussed and example technologies are presented. Potential applications are defined in the context of the nuclear material and weapons lifecycle. Example applications range from authentication (e.g., tracking and signatures within the chain of custody from downloading through weapons storage, unclassified templates and unique identification) to verification of absence and final material disposition.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗

Mechanisms of a novel regulatory light chain–dependent cardiac myosin inhibitor

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the heart characterized by thickening of the left ventricle (LV), hypercontractility, and impaired relaxation. HCM is caused primarily by heritable mutations in sarcomeric proteins, such as β myosin heavy chain. Until recently, medications in clinical use for HCM did not directly target the underlying contractile changes in the sarcomere. Here, we investigate a novel small molecule, RLC-1, identified in a bovine cardiac myofibril high-throughput screen. RLC-1 is highly dependent on the presence of a regulatory light chain to bind to cardiac myosin and modulate its ATPase activity. In demembranated rat LV trabeculae, RLC-1 decreased maximal Ca2+-activated force and Ca2+ sensitivity of force, while it increased the submaximal rate constant for tension redevelopment. In myofibrils isolated from rat LV, both maximal and submaximal Ca2+-activated force are reduced by nearly 50%. Additionally, the fast and slow phases of relaxation were approximately twice as fast as DMSO controls, and the duration of the slow phase was shorter. Structurally, x-ray diffraction studies showed that RLC-1 moved myosin heads away from the thick filament backbone and decreased the order of myosin heads, which is different from other myosin inhibitors. In intact trabeculae and isolated cardiomyocytes, RLC-1 treatment resulted in decreased peak twitch magnitude and faster activation and relaxation kinetics. In conclusion, RLC-1 accelerated kinetics and decreased force production in the demembranated tissue, intact tissue, and intact whole cells, resulting in a smaller cardiac twitch, which could improve the underlying contractile changes associated with HCM.

Physiology↗

EVOLUTION OF RELATIVISTIC PLASMOID CHAINS IN A POYNTING-DOMINATED PLASMA

In this paper, we investigate the evolution of plasmoid chains in a Poynting-dominated plasma. We model the relativistic current sheet with a cold background plasma using the relativistic resistive magnetohydrodynamic approximation and solve for its temporal evolution numerically. We perform various calculations using different magnetization parameters of the background plasma and different Lundquist numbers. Numerical results show that the initially induced plasmoid triggers a secondary tearing instability, which gradually fills the current sheet with plasmoids, as has also been observed in the non-relativistic case. We find that plasmoid chains greatly enhance the reconnection rate, which becomes independent of the Lundquist number when the Lundquist number exceeds a critical value. In addition, we show that the distribution of plasmoid size becomes a power law. Since magnetic reconnection is expected to play an important role in various high-energy astrophysical phenomena, our results can be used for explaining the physical mechanisms of those phenomena.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Probing magnetic order and disorder in the one-dimensional molecular spin chains CuF2(pyz) and [Ln(hfac)(3)(boaDTDA)](n) (Ln = Sm, La) using implanted muons.

We present the results of muon-spin relaxation (mu+SR) measurements on antiferromagnetic and ferromagnetic spin chains. In antiferromagnetic CuF2(pyz) we identify a transition to long range magnetic order taking place at T-N = 0.6(1) K, allowing us to estimate a ratio with the intrachain exchange of T-N/vertical bar J vertical bar approximate to 0.1 and the ratio of interchain to intrachain exchange coupling as vertical bar J'/J vertical bar approximate to 0.05. The ferromagnetic chain [Sm(hfac)(3)(boaDTDA)](n) undergoes an ordering transition at T-c = 2.8(1) K, seen via a broad freezing of dynamic fluctuations on the muon (microsecond) timescale and implying T-c/vertical bar J vertical bar approximate to 0.6. The ordered radical moment continues to fluctuate on this timescale down to 0.3 K, while the Sm moments remain disordered. In contrast, the radical spins in [La(hfac)(3)(boaDTDA)](n) remain magnetically disordered down to T = 0.1 K suggesting T-c/vertical bar J vertical bar < 0.17.

muon-spin relaxation↗

The GGE averaged currents of the classical Toda chain

The Toda chain with random initial data is studied. Of particular interest are generalized Gibbs ensembles, their averaged conserved fields, and the averages of the corresponding currents. While averaged fields are well-understood, the description of averaged currents has hitherto relied on the collision-rate assumption. For the Toda chain, the rate assumption can be investigated numerically. Here, we provide convincing evidence for the validity of the rate assumption. This lends further support to the idea that generalized Euler-type equations have a structure common to all integrable extensive systems.

97 MATHEMATICS AND COMPUTING↗

INFLATING A CHAIN OF X-RAY-DEFICIENT BUBBLES BY A SINGLE JET ACTIVITY EPISODE

We show that a continuous jet with time-independent launching properties can inflate a chain of close and overlapping X-ray deficient bubbles. Using the numerical code PLUTO we run 2.5D (i.e., a spherical coordinate system with cylindrical symmetry) hydrodynamic simulations and study the interaction of the jets with the intracluster medium. A key process is vortex fragmentation due to several mechanisms, including vortex-shedding and Kelvin-Helmholtz instabilities. Our results can account for the structure of two opposite chains of close bubbles as observed in the galaxy cluster Hydra A. Our results imply that the presence of multiple pairs of bubbles does not necessarily imply several jet-launching episodes. This finding might have implications for feedback mechanisms operating by jets.

79 ASTRONOMY AND ASTROPHYSICS↗

Implementation of a practical Markov chain Monte Carlo sampling algorithm in PyBioNetFit

Abstract Summary Bayesian inference in biological modeling commonly relies on Markov chain Monte Carlo (MCMC) sampling of a multidimensional and non-Gaussian posterior distribution that is not analytically tractable. Here, we present the implementation of a practical MCMC method in the open-source software package PyBioNetFit (PyBNF), which is designed to support parameterization of mathematical models for biological systems. The new MCMC method, am, incorporates an adaptive move proposal distribution. For warm starts, sampling can be initiated at a specified location in parameter space and with a multivariate Gaussian proposal distribution defined initially by a specified covariance matrix. Multiple chains can be generated in parallel using a computer cluster. We demonstrate that am can be used to successfully solve real-world Bayesian inference problems, including forecasting of new Coronavirus Disease 2019 case detection with Bayesian quantification of forecast uncertainty. Availability and implementation PyBNF version 1.1.9, the first stable release with am, is available at PyPI and can be installed using the pip package-management system on platforms that have a working installation of Python 3. PyBNF relies on libRoadRunner and BioNetGen for simulations (e.g. numerical integration of ordinary differential equations defined in SBML or BNGL files) and Dask.Distributed for task scheduling on Linux computer clusters. The Python source code can be freely downloaded/cloned from GitHub and used and modified under terms of the BSD-3 license (https://github.com/lanl/pybnf). Online documentation covering installation/usage is available (https://pybnf.readthedocs.io/en/latest/). A tutorial video is available on YouTube (https://www.youtube.com/watch?v=2aRqpqFOiS4&t=63s). Supplementary information Supplementary data are available at Bioinformatics online.

59 BASIC BIOLOGICAL SCIENCES↗

Elucidation of complex respiratory chains: a straightforward strategy to monitor electron transfer between cytochromes

Abstract Cytochromes are electron transfer (ET) proteins essential in various biological systems, playing crucial roles in the respiratory chains of bacteria. These proteins are particularly abundant in electrogenic microorganisms and are responsible for the efficient delivery of electrons to the cells’ exterior. The capability of sending electrons outside the cells open new avenues to be explored for emerging biotechnological applications in bioremediation, microbial electrosynthesis, and bioenergy fields. To develop these applications, it is critical to identify the different redox partners and to elucidate the stepwise ET along the respiratory paths. However, investigating direct ET events between proteins with identical features in nearly all spectroscopic techniques is extremely challenging. Nuclear magnetic resonance (NMR) spectroscopy offers the possibility to overcome this difficulty by analysing the alterations of the spectral signatures of each protein caused by electron exchange events. The uncrowded NMR spectral regions containing the heme resonances of the cytochromes display unique and distinct signatures in the reduced and oxidized states, which can be explored to monitor ET within the redox complex. In this study, we present a strategy for a fast and straightforward monitorization of ET between c-type cytochromes, using as model a triheme periplasmic cytochrome and a membrane-associated monoheme cytochrome from the electrogenic bacterium Geobacter sulfurreducens. The comparison between the 1D 1H NMR spectra obtained for samples containing the two cytochromes and for samples containing the individual proteins clearly demonstrated a unidirectional ET within the redox complex. This strategy provides a simple and straightforward means to elucidate complex biologic respiratory ET chains.

Morgado, Leonor (ORCID:0000000237605180)↗

Applying Crystallography and 19 F NMR to investigate dynamics and partner protein interactions in a long chain Flavodoxin

Flavodoxin (Fld) is a small FMN containing protein that is involved in single electron transfer. The long‐chain flavodoxin in Rhodopseudomonas palustris bacteria replaces ferredoxin as a low‐potential electron carrier when iron is scarce. Thus it is proposed to interact with the bifurcating electron transfer flavoprotein (ETF) that yields low‐potential electrons. A surface loop on Fld interacts with another of Fld's partner proteins, so we hypothesize that it also mediates Fld's interaction with ETF. To monitor interactions with ETF directly and investigate dynamics in this loop, we are using 19 F NMR in solution. 19 F is hyperresponsive to changes in its chemical environment with a chemical shift range of >300 ppm. To provide a static reference point and assess structural heterogeneity, we are also exploiting X‐ray crystallography. In this study we selectively fluorinated the five tyrosine residues in Fld. We obtained resonance assignments from 19 F spectra of Fld variants in which individual tyrosine residues have been replaced. We obtain well resolved signals for each residue, but the resonances' linewidths indicate dynamics that affects some resonances more than others. Y90 residue displays two resonances demonstrating two different conformations that interconvert slowly on an NMR time scale. Meanwhile the crystal structure solved at 2.1Å resolution reveals two molecules per asymmetric unit providing two perspectives on the details of the structure. The crystal symmetry is monoclinic in contrast to most of the other Flds, which are orthorhombic. Interestingly, the long loop bearing Y121 and Y123 is not well resolved in chain B of the crystal structure, and the NMR line of Y123 is exceptionally broad, both indicating that the loop is dynamic and capable of altering its conformation to accomodate binding to a partner protein. Future directions include monitoring the changes in the 19 F NMR of the Fld when titrated with the partner protein, temperature dependence of the NMR spectrum and relaxation studies to evaluate time scales of motions.

Khan, Sharique↗

Unconventional critical behavior in the quasi-one-dimensional S=1 chain NiTe 2 O 5

In this work, we report a new quasi-one-dimensional S = 1 chain compound NiTe 2 O 5 . From the comprehensive study of the structure and magnetic properties on high quality single crystalline NiTe 2 O 5 , it’s revealed that NiTe 2 O 5 undergoes a transition into an intriguing long-range antiferromagnetic order at T N = 30.5 K, in which longitudinal magnetic moments along the chain direction are ferromagnetically ordered, while their transverse components have an alternating ferromagnetic-antiferromagnetic coupling. Even though the temperature dependence of magnetic susceptibility represents an archetypal anisotropic antiferromagnetic order, we found that critical behavior of unconventional nature with α'~0.25 and β~0.18 is accompanied by the temperature evolution of the antiferromagnetic order parameter.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Complex magnetic order in the decorated spin-chain system Rb 2 Mn 3 ( MoO 4 ) 3 ( OH ) 2

The macroscopic magnetic properties and microscopic magnetic structure of Rb 2 Mn 3 (MoO 4 ) 3 (OH) 2 (space group Pn ma) are investigated by magnetization, heat capacity, and single-crystal neutron diffraction measurements. The compound's crystal structure contains bond-alternating [Mn 3 O 11 ] ∞ chains along the b axis, formed by isosceles triangles of Mn ions occupying two crystallographically nonequivalent sites (the Mn1 site on the base and Mn2 site on the vertex). These chains are only weakly linked to each other by nonmagnetic oxyanions. Both superconducting quantum interference device magnetometry and neutron diffraction experiments show two successive magnetic transitions as a function of temperature. On cooling, it transitions from a paramagnetic phase into an incommensurate phase below 4.5 K with a magnetic wave vector near k 1 = ( 0 , 0.46 , 0 ). An additional commensurate antiferromagnetically ordered component arises with k 2 = ( 0, 0, 0), forming a complex magnetic structure below 3.5 K with two different propagation vectors of different stars. On further cooling, the incommensurate wave vector undergoes a lock-in transition below 2.3 K. The experimental results suggest that the magnetic superspace group is Pnma. 1' (0b0) s0ss for the single- k incommensurate phase and is Pn' m a ( 0 b 0 ) 00 s for the two- k magnetic phase. We propose a simplified magnetic structure model taking into account the major ordered contributions, where the commensurate k 2 defines the ordering of the c-axis component of the Mn1 magnetic moment, while the incommensurate k 1 describes the ordering of the ab -plane components of both Mn1 and Mn2 moments into elliptical cycloids.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Lyapunov growth in quantum spin chains

The Ising spin chain with longitudinal and transverse magnetic fields is often used in studies of quantum chaos, displaying both chaotic and integrable regions in its parameter space. However, even at a strongly chaotic point this model does not exhibit Lyapunov growth of the commutator squared of spin operators, as this observable saturates before exponential growth can manifest itself (even in situations where a spatial suppression factor makes the initial commutator small). In this work, we extend this model from the spin 1/2 Ising model to higher spins, demonstrate numerically that a window of exponential growth opens up for sufficiently large spin, and extract a quantity which corresponds to a notion of a Lyapunov exponent. In the classical infinite-spin limit, we identify and compute the appropriate classical analog of the commutator squared, and show that the corresponding exponent agrees with the infinite-spin limit extracted from the quantum spin chain.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Beyond universal behavior in the one-dimensional chain with random nearest-neighbor hopping

Here, we study the one-dimensional nearest-neighbor tight-binding model of electrons with independently distributed random hopping and no on-site potential (i.e., off-diagonal disorder with particle-hole symmetry, leading to sublattice symmetry, for each realization). For nonsingular distributions of the hopping, it is known that the model exhibits a universal, singular behavior of the density of states $ρ(E) ~ 1/|E\: \text{ln}^3 |E||$ and of the localization length $ξ(E) ~ |\text{ln}|E||$, near the band center $\textit{E}$ = 0 . (This singular behavior is also applicable to random $\textit{XY}$ and Heisenberg spin chains; it was first obtained by Dyson for a specific random harmonic oscillator chain.) Simultaneously, the state at$\textit{E}$ = 0 shows a universal, subexponential decay at large distances $\sim \text{exp}[–\sqrt{r/r_0}]$. In this study, we consider singular, but normalizable, distributions of hopping, whose behavior at small $\textit{t}$ is of the form $\sim 1/[t \text{ln}^{λ+1}(1/t)]$, characterized by a single, continuously tunable parameter λ > 0. We find, using a combination of analytic and numerical methods, that while the universal result applies for λ > 2, it no longer holds in the interval 0 < λ < 2. In particular, we find that the form of the density of states singularity is enhanced (relative to the Dyson result) in a continuous manner depending on the nonuniversal parameter λ; simultaneously, the localization length shows a less divergent form at low energies and ceases to diverge below λ = 1. For λ < 2, the fall-off of the $\textit{E}$ = 0 state at large distances also deviates from the universal result and is of the form $\sim\text{exp}[–(r/r_0)^{1/λ}]$ , which decays faster than an exponential for λ < 1.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Spinon excitations in the quasi-one-dimensional $S = \frac{1}{2}$ chain compound Cs 4 CuSb 2 Cl 12

The spin-$\frac{1}{2}$ Heisenberg antiferromagnetic chain is ideal for realizing one of the simplest gapless quantum spin liquids (QSLs), supporting a many-body ground state whose elementary excitations are fractional fermionic excitations called spinons. Here we report the discovery of such a one-dimensional (1D) QSL in Cs 4 CuSb 2 Cl 12 . Compared to previously reported $S = \frac{1}{2}$ 1D chains, this material possesses a wider temperature range over which the QSL state is stabilized. In this work, we identify spinon excitations extending at $\textit{T}$ > 0.8 K, with a large $\textit{T}$-linear contribution to the specific heat, γ = 31.5(2)mJ mol –1 K –2 , which contribute itinerantly to thermal transport up to temperatures as high as $\textit{T}$ = 35 K. At $\textit{T}$ = 0.7 K , we find a second-order phase transition that is unchanged by a $μ_0H = 5T$ magnetic field. Cs 4 CuSb 2 Cl 12 reveals new phenomenology deep in the 1D QSL regime, supporting a gapped QSL phase over a wide temperature range compared to many other experimental realizations.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Low-energy physics of isotropic spin-1 chains in the critical and Haldane phases

Using a matrix product state algorithm with infinite boundary conditions, we compute high-resolution dynamic spin and quadrupolar structure factors in the thermodynamic limit to explore the low-energy excitations of isotropic bilinear-biquadratic spin-1 chains. Haldane mapped the spin-1 Heisenberg antiferromagnet to a continuum field theory, the nonlinear sigma model (NLσM). In this work, we find that the NLσM fails to capture the influence of the biquadratic term and provides only an unsatisfactory description of the Haldane phase physics. But several features in the Haldane phase can be explained by noninteracting multimagnon states. The physics at the Uimin-Lai-Sutherland point is characterized by multisoliton continua. Moving into the extended critical phase, we find that these excitation continua contract, which we explain using a field-theoretic description. New excitations emerge at higher energies and, in the vicinity of the purely biquadratic point, they show simple cosine dispersions. Using block fidelities, we identify them as elementary one-particle excitations and relate them to the integrable Temperley-Lieb chain.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Nonlinear soliton confinement in weakly coupled antiferromagnetic spin chains

In this work, we analyze the low-energy dynamics of quasi-one-dimensional, large-$\textit{S}$ quantum antiferromagnets with easy-axis anisotropy, using a semiclassical nonlinear sigma model. The saddle point approximation leads to a sine-Gordon equation which supports soliton solutions. These correspond to the movement of spatially extended domain walls. Long-range magnetic order is a consequence of a weak interchain coupling. Below the ordering temperature, the coupling to nearby chains leads to an energy cost associated with the separation of two domain walls. From the kink-antikink two-soliton solution, we compute the effective confinement potential. At distances large compared to the size of the solitons the potential is linear, as expected for pointlike domain walls. At small distances the gradual annihilation of the solitons weakens the effective attraction and renders the potential quadratic. From numerically solving the effective one-dimensional Schrödinger equation with this nonlinear confinement potential we compute the soliton bound state spectrum. We apply the theory to CaFe 2 O 4 , an anisotropic $\textit{S}$ = 5/2 magnet based upon antiferromagnetic zigzag chains. Using inelastic neutron scattering, we are able to resolve seven discrete energy levels for spectra recorded slightly below the Néel temperature $T_N$ ≈ 200 K. These modes are well described by our nonlinear confinement model in the regime of large spatially extended solitons.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

One-directional polarization transport in electron/nuclear spin chains with loss and gain

Understanding the joint dynamics of electron and nuclear spins is central to core concepts in solid-state magnetic resonance such as spin-lattice relaxation and dynamic nuclear polarization, but a generalization that capitalizes on competing polarization loss and gain channels is still lacking. Here, we study theoretically the non-Hermitian dynamics of hybrid electron/nuclear spin systems in the simultaneous presence of electron spin pumping and spin-lattice relaxation. Focusing on periodic, one-dimensional chains, we find that, by adjusting the electron spin pumping to a critical level, it is possible to steer the flow of nuclear polarization to create site-dependent distributions where either end of the array polarizes in opposite ways, irrespective of the initial state. By contrast, we show that ring-like patterns—where the limit nuclear polarization is uniform—exhibit a non-decaying, externally driven nuclear spin current. Interestingly, cyclic magnetic field modulation can render these processes largely robust to defects in the chain, a response featuring some interesting similarities—and differences—with recent findings in other non-Hermitian physical platforms.

36 MATERIALS SCIENCE↗