Concerted 2-5A-Mediated mRNA Decay and Transcription Reprogram Protein Synthesis in the dsRNA Response.

Viral and endogenous double-stranded RNA (dsRNA) is a potent trigger for programmed RNA degradation by the 2-5A/RNase L complex in cells of all mammals. This 2-5A-mediated decay (2-5AMD) is a conserved stress response switching global protein synthesis from homeostasis to production of interferons (IFNs). To understand this mechanism, we examined 2-5AMD in human cells and found that it triggers polysome collapse characteristic of inhibited translation initiation. We determined that translation initiation complexes and ribosomes purified from translation-arrested cells remain functional. However, spike-in RNA sequencing (RNA-seq) revealed cell-wide decay of basal mRNAs accompanied by rapid accumulation of mRNAs encoding innate immune proteins. Our data attribute this 2-5AMD evasion to better stability of defense mRNAs and positive feedback in the IFN response amplified by RNase L-resistant molecules. We conclude that 2-5AMD and transcription act in concert to refill mammalian cells with defense mRNAs, thereby "prioritizing" the synthesis of innate immune proteins.

Thermal robustness of signaling in bacterial chemotaxis.

Temperature is a global factor that affects the performance of all intracellular networks. Robustness against temperature variations is thus expected to be an essential network property, particularly in organisms without inherent temperature control. Here, we combine experimental analyses with computational modeling to investigate thermal robustness of signaling in chemotaxis of Escherichia coli, a relatively simple and well-established model for systems biology. We show that steady-state and kinetic pathway parameters that are essential for chemotactic performance are indeed temperature-compensated in the entire physiological range. Thermal robustness of steady-state pathway output is ensured at several levels by mutual compensation of temperature effects on activities of individual pathway components. Moreover, the effect of temperature on adaptation kinetics is counterbalanced by preprogrammed temperature dependence of enzyme synthesis and stability to achieve nearly optimal performance at the growth temperature. Similar compensatory mechanisms are expected to ensure thermal robustness in other systems.

piRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting.

Small noncoding RNAs such as piRNAs are guides for Argonaute proteins, enabling sequence-specific, post-transcriptional regulation of gene expression. The piRNAs of Caenorhabditis elegans have been observed to bind targets with high mismatch tolerance and appear to lack specific transposon targets, unlike piRNAs in Drosophila melanogaster and other organisms. These observations support a model in which C. elegans piRNAs provide a broad, indiscriminate net of silencing, competing with siRNAs associated with the CSR-1 Argonaute that specifically protect self-genes from silencing. However, the breadth of piRNA targeting has not been subject to in-depth quantitative analysis, nor has it been explained how piRNAs are distributed across sequence space to achieve complete coverage. Through a bioinformatic analysis of piRNA sequences, incorporating an original data-based metric of piRNA-target distance, we demonstrate that C. elegans piRNAs are functionally random, in that their coverage of sequence space is comparable to that of random sequences. By possessing a sufficient number of distinct, essentially random piRNAs, C. elegans is able to target arbitrary nonself sequences with high probability. We extend this approach to a selection of other nematodes, finding results which elucidate the mechanism by which nonself mRNAs are silenced, and have implications for piRNA evolution and biogenesis.

Realistic Protocol to Measure Entanglement at Finite Temperatures.

It is desirable to relate entanglement of many-body systems to measurable observables. In systems with a conserved charge, it was recently shown that the number entanglement entropy (NEE)-i.e., the entropy change due to an unselective subsystem charge measurement-is an entanglement monotone. Here we derive finite-temperature equilibrium relations between Rényi moments of the NEE, and multipoint charge correlations. These relations are exemplified in quantum dot systems where the desired charge correlations can be measured via a nearby quantum point contact. In quantum dots recently realizing the multichannel Kondo effect we show that the NEE has a nontrivial universal temperature dependence which is now accessible using the proposed methods.

Identifying an Environment-Induced Localization Transition from Entropy and Conductance.

Environment-induced localization transitions (LT) occur when a small quantum system interacts with a bath of harmonic oscillators. At equilibrium, LTs are accompanied by an entropy change, signaling the loss of coherence. Despite extensive efforts, equilibrium LTs have yet to be observed. Here, we demonstrate that ongoing experiments on double quantum dots that measure entropy using a nearby quantum point contact realize the celebrated spin-boson model and allow to measure the entropy change of its LT. We find a Kosterlitz-Thouless flow diagram, leading to a universal jump in the spin-bath interaction, reflected in a discontinuity in the zero temperature QPC conductance.

Erratum: Mechanical Frustration of Phase Separation in the Cell Nucleus by Chromatin [Phys. Rev. Lett. 126, 258102 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.258102.

Fractional Entropy of Multichannel Kondo Systems from Conductance-Charge Relations.

Fractional entropy is a signature of nonlocal degrees of freedom, such as Majorana zero modes or more exotic non-Abelian anyons. Although direct experimental measurements remain challenging, Maxwell relations provide an indirect route to the entropy through charge measurements. Here we consider multichannel charge-Kondo systems, which are predicted to host exotic quasiparticles due to a frustration of Kondo screening at low temperatures. In the absence of experimental data for the charge occupation, we derive relations connecting the latter to the conductance, for which experimental results have recently been obtained. Our analysis indicates that Majorana and Fibonacci anyon quasiparticles are well developed in existing two- and three-channel charge-Kondo devices, and that their characteristic k_{B}logsqrt[2] and k_{B}log[(1+sqrt[5])/2] entropies are experimentally measurable.

Entropy Measurement of a Strongly Coupled Quantum Dot.

The spin 1/2 entropy of electrons trapped in a quantum dot has previously been measured with great accuracy, but the protocol used for that measurement is valid only within a restrictive set of conditions. Here, we demonstrate a novel entropy measurement protocol that is universal for arbitrary mesoscopic circuits and apply this new approach to measure the entropy of a quantum dot hybridized with a reservoir. The experimental results match closely to numerical renormalization group (NRG) calculations for small and intermediate coupling. For the largest couplings investigated in this Letter, NRG calculations predict a suppression of spin entropy at the charge transition due to the formation of a Kondo singlet, but that suppression is not observed in the experiment.

Motif-pattern dependence of biomolecular phase separation driven by specific interactions.

Eukaryotic cells partition a wide variety of important materials and processes into biomolecular condensates-phase-separated droplets that lack a membrane. In addition to nonspecific electrostatic or hydrophobic interactions, phase separation also depends on specific binding motifs that link together constituent molecules. Nevertheless, few rules have been established for how these ubiquitous specific, saturating, motif-motif interactions drive phase separation. By integrating Monte Carlo simulations of lattice-polymers with mean-field theory, we show that the sequence of heterotypic binding motifs strongly affects a polymer's ability to phase separate, influencing both phase boundaries and condensate properties (e.g. viscosity and polymer diffusion). We find that sequences with large blocks of single motifs typically form more inter-polymer bonds, which promotes phase separation. Notably, the sequence of binding motifs influences phase separation primarily by determining the conformational entropy of self-bonding by single polymers. This contrasts with systems where the molecular architecture primarily affects the energy of the dense phase, providing a new entropy-based mechanism for the biological control of phase separation.

Mechanical Frustration of Phase Separation in the Cell Nucleus by Chromatin.

Liquid-liquid phase separation is a fundamental mechanism underlying subcellular organization. Motivated by the striking observation that optogenetically generated droplets in the nucleus display suppressed coarsening dynamics, we study the impact of chromatin mechanics on droplet phase separation. We combine theory and simulation to show that cross-linked chromatin can mechanically suppress droplets' coalescence and ripening, as well as quantitatively control their number, size, and placement. Our results highlight the role of the subcellular mechanical environment on condensate regulation.

Odd and even Kondo effects from emergent localization in quantum point contacts.

A quantum point contact (QPC) is a basic nanometre-scale electronic device: a short and narrow transport channel between two electron reservoirs. In clean channels, electron transport is ballistic and the conductance is then quantized as a function of channel width with plateaux at integer multiples of 2e(2)/h (where e is the electron charge and h is Planck's constant). This can be understood in a picture where the electron states are propagating waves, without the need to account for electron-electron interactions. Quantized conductance could thus be the signature of ultimate control over nanoscale electron transport. However, even studies with the cleanest QPCs generically show significant anomalies in the quantized conductance traces, and there is consensus that these result from electron many-body effects. Despite extensive experimental and theoretical studies, understanding these anomalies is an open problem. Here we report that the many-body effects have their origin in one or more spontaneously localized states that emerge from Friedel oscillations in the electron charge density within the QPC channel. These localized states will have electron spins associated with them, and the Kondo effect--related to electron transport through such localized electron spins--contributes to the formation of the many-body state. We present evidence for such localization, with Kondo effects of odd or even character, directly reflecting the parity of the number of localized states; the evidence is obtained from experiments with length-tunable QPCs that show a periodic modulation of the many-body properties with Kondo signatures that alternate between odd and even Kondo effects. Our results are of importance for assessing the role of QPCs in more complex hybrid devices and for proposals for spintronic and quantum information applications. In addition, our results show that tunable QPCs offer a versatile platform for investigating many-body effects in nanoscale systems, with the ability to probe such physics at the level of a single site.

Spontaneous Breakdown of Topological Protection in Two Dimensions.

Because of time-reversal symmetry, two-dimensional topological insulators support counterpropagating helical edge modes. Here we show that, unlike the infinitely sharp edge potential utilized in traditional calculations, an experimentally more realistic smooth edge potential gives rise to edge reconstruction and, consequently, spontaneous time-reversal symmetry breaking. Such edge reconstruction may lead to breaking of the expected perfect conductance quantization, to a finite Hall resistance at zero magnetic field, and to a spin current. This calculation underpins the fragility of the topological protection in realistic systems, which is of crucial importance in proposed applications.

Condensation and localization of the partitioning protein ParB on the bacterial chromosome.

The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB-DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein-DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB-DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB-DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB-DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes.

Band of critical States in anderson localization in a strong magnetic field with random spin-orbit scattering.

The Anderson localization problem for a noninteracting two-dimensional electron gas subject to a strong magnetic field, disordered potential, and spin-orbit coupling is studied numerically on a square lattice. The nature of the corresponding localization-delocalization transition and the properties of the pertinent extended states depend on whether the spin-orbit coupling is uniform or fully random. For uniform spin-orbit coupling (such as Rashba coupling due to a uniform electric field), there is a band of metallic extended states in the center of a Landau band as in a "standard" Anderson metal-insulator transition. However, for fully random spin-orbit coupling, the familiar pattern of Landau bands disappears. Instead, there is a central band of critical states with definite fractal structure separated at two critical energies from two side bands of localized states. Moreover, finite size scaling analysis suggests that for this novel transition, on the localized side of a critical energy E_{c}, the localization length diverges as ξ(E)∝exp(α/sqrt[|E-E_{c}|]), a behavior which, together with the emergence of a band of critical states, is reminiscent of a Berezinskii-Kosterlitz-Thouless transition.

The value of information gathering in phage-bacteria warfare.

Phages-viruses that infect bacteria-have evolved over billions of years to overcome bacterial defenses. Temperate phage, upon infection, can "choose" between two pathways: lysis-in which the phage create multiple new phage particles, which are then liberated by cell lysis, and lysogeny-where the phage's genetic material is added to the bacterial DNA and transmitted to the bacterial progeny. It was recently discovered that some phages can read information from the environment related to the density of bacteria or the number of nearby infection attempts. Such information may help phage make the right choice between the two pathways. Here, we develop a theoretical model that allows an infecting phage to change its strategy (i.e. the ratio of lysis to lysogeny) depending on an outside signal, and we find the optimal strategy that maximizes phage proliferation. While phages that exploit extra information naturally win in competition against phages with a fixed strategy, there may be costs to information, e.g. as the necessary extra genes may affect the growth rate of a lysogen or the burst size of new phage for the lysis pathway. Surprisingly, even when phages pay a large price for information, they can still maintain an advantage over phages that lack this information, indicating the high benefit of intelligence gathering in phage-bacteria warfare.

Lytic and temperate phage naturally coexist in a dynamic population model.

When phage infect their bacterial hosts, they may either lyse the cell and generate a burst of new phage, or lysogenize the bacterium, incorporating the phage genome into it. Phage lysis/lysogeny strategies are assumed to be highly optimized, with the optimal tradeoff depending on environmental conditions. However, in nature, phage of radically different lysis/lysogeny strategies coexist in the same environment, preying on the same bacteria. How can phage preying on the same bacteria coexist if one is more optimal than the other? Here, we address this conundrum within a modeling framework, simulating the population dynamics of communities of phage and their lysogens. We find that coexistence between phage of different lysis/lysogeny strategies is a natural outcome of chaotic population dynamics that arise within sufficiently diverse communities, which ensure no phage is able to absolutely dominate its competitors. Our results further suggest a bet-hedging mechanism at the level of the phage pan-genome, wherein obligate lytic (virulent) strains typically outcompete temperate strains, but also more readily fluctuate to extinction within a local community.

Proposed measurement of spatial correlations at the Berezinski-Kosterlitz-Thouless transition of superconducting thin films.

The Berezinski-Kosterlitz-Thouless transition is a unique two-dimensional phase transition, separating two phases with exponentially and power-law decaying correlations, respectively. In disordered systems, these correlations propagate along favorable paths, with the transition marking the point where global coherence is lost. Here we propose an experimental method to probe locally these particular paths in superconducting thin films, which exhibit this transition, and demonstrate theoretically that close to the transition the coherence propagates along a ramified network, reminiscent of a percolation transition. We suggest and calculate experimentally accessible quantities that can shed light on the spatial correlations in the system as it approaches the critical point. This approach can be applicable to a variety of phase transitions in disordered systems.

Edge reconstruction in the ν=2/3 fractional quantum Hall state.

The edge structure of the ν=2/3 fractional quantum Hall state has been studied for several decades, but recent experiments, exhibiting upstream neutral mode(s), a plateau at a Hall conductance of 1/3(e2/h) through a quantum point contact, and a crossover of the effective charge, from e/3 at high temperature to 2e/3 at low temperature, could not be explained by a single theory. Here we develop such a theory, based on edge reconstruction due to a confining potential with finite slope, that admits an additional ν=1/3 incompressible strip near the edge. Renormalization group analysis of the effective edge theory due to disorder and interactions explains the experimental observations.

Chemical sensing by nonequilibrium cooperative receptors.

Cooperativity arising from local interactions in equilibrium receptor systems provides gain, but does not increase sensory performance, as measured by the signal-to-noise ratio (SNR) due to a fundamental tradeoff between gain and intrinsic noise. Here we allow sensing to be a nonequilibrium process and show that energy dissipation cannot circumvent the fundamental tradeoff, so that the SNR is still optimal for independent receptors. For systems requiring high gain, nonequilibrium 2D-coupled receptors maximize the SNR, revealing a new design principle for biological sensors.

Nature of the superconductor-insulator transition in disordered superconductors.

The interplay of superconductivity and disorder has intrigued scientists for several decades. Disorder is expected to enhance the electrical resistance of a system, whereas superconductivity is associated with a zero-resistance state. Although superconductivity has been predicted to persist even in the presence of disorder, experiments performed on thin films have demonstrated a transition from a superconducting to an insulating state with increasing disorder or magnetic field. The nature of this transition is still under debate, and the subject has become even more relevant with the realization that high-transition-temperature (high-T(c)) superconductors are intrinsically disordered. Here we present numerical simulations of the superconductor-insulator transition in two-dimensional disordered superconductors, starting from a microscopic description that includes thermal phase fluctuations. We demonstrate explicitly that disorder leads to the formation of islands where the superconducting order is high. For weak disorder, or high electron density, increasing the magnetic field results in the eventual vanishing of the amplitude of the superconducting order parameter, thereby forming an insulating state. On the other hand, at lower electron densities or higher disorder, increasing the magnetic field suppresses the correlations between the phases of the superconducting order parameter in different islands, giving rise to a different type of superconductor-insulator transition. One of the important predictions of this work is that in the regime of high disorder, there are still superconducting islands in the sample, even on the insulating side of the transition. This result, which is consistent with experiments, explains the recently observed huge magneto-resistance peak in disordered thin films and may be relevant to the observation of 'the pseudogap phenomenon' in underdoped high-T(c) superconductors.