Continuous B- to A- Transition in Protein-DNA Binding - How Well Is It Described by Current AMBER Force Fields?

When DNA interacts with a protein, its structure often undergoes significant conformational adaptation. Perhaps the most common is the transition from canonical B-DNA towards the A-DNA form, which is not a two-state, but rather a continuous transition. The A- and B- forms differ mainly in sugar pucker P (north/south) and glycosidic torsion χ (high-anti/anti). The combination of A-like P and B-like χ (and vice versa) represents the nature of the intermediate states lying between the pure A- and B- forms. In this work, we study how the A/B equilibrium and in particular the A/B intermediate states, which are known to be over-represented at protein-DNA interfaces, are modeled by current AMBER force fields. Eight protein-DNA complexes and their naked (unbound) DNAs were simulated with OL15 and bsc1 force fields as well as an experimental combination OL15χOL3. We found that while the geometries of the A-like intermediate states in the molecular dynamics (MD) simulations agree well with the native X-ray geometries found in the protein-DNA complexes, their populations (stabilities) are significantly underestimated. Different force fields predict different propensities for A-like states growing in the order OL15 < bsc1 < OL15χOL3, but the overall populations of the A-like form are too low in all of them. Interestingly, the force fields seem to predict the correct sequence-dependent A-form propensity, as they predict larger populations of the A-like form in naked (unbound) DNA in those steps that acquire A-like conformations in protein-DNA complexes. The instability of A-like geometries in current force fields may significantly alter the geometry of the simulated protein-DNA complex, destabilize the binding motif, and reduce the binding energy, suggesting that refinement is needed to improve description of protein-DNA interactions in AMBER force fields.

First-Order Phase Transformation at Constant Volume: A Continuous Transition?

We describe a first-order phase transition of a simple system in a process where the volume is kept constant. We show that, unlike what happens when the pressure is constant, (i) the transformation extends over a finite temperature (and pressure) range, (ii) each and every extensive potential (internal energy U, enthalpy H, Helmholtz energy F, and Gibbs energy G), and the entropy S is continuous across the transition, and (iii) the constant-volume heat capacity does not diverge during the transition and only exhibits discrete jumps. These non-intuitive results highlight the importance of controlling the correct variables in order to distinguish between continuous and discontinuous transitions. We apply our results to describe the transition between ice VI and liquid water using thermodynamic information available in the literature and also to show that a first-order phase transition driven in isochoric condition can be used as the operating principle of a mechanical actuator.

Weak Multiplex Percolation

In many systems consisting of interacting subsystems, the complex interactions between elements can be represented using multilayer networks. However percolation, key to understanding connectivity and robustness, is not trivially generalised to multiple layers. This Element describes a generalisation of percolation to multilayer networks: weak multiplex percolation. A node belongs to a connected component if at least one of its neighbours in each layer is in this component. The authors fully describe the critical phenomena of this process. In two layers with finite second moments of the degree distributions the authors observe an unusual continuous transition with quadratic growth above the threshold. When the second moments diverge, the singularity is determined by the asymptotics of the degree distributions, creating a rich set of critical behaviours. In three or more layers the authors find a discontinuous hybrid transition which persists even in highly heterogeneous degree distributions, becoming continuous only when the powerlaw exponent reaches $1+1/(M-1)$ for $M$ layers.

Higher-order synchronization on the sphere

We construct a system of $N$ interacting particles on the unit sphere $S^{d-1}$ in $d$-dimensional space, which has $d$-body interactions only. The equations have a gradient formulation derived from a rotationally-invariant potential of a determinantal form summed over all nodes, with antisymmetric coefficients. For $d=3$, for example, all trajectories lie on the $2$-sphere and the potential is constructed from the triple scalar product summed over all oriented $2$-simplices. We investigate the cases $d=3,4,5$ in detail, and find that the system synchronizes from generic initial values, for both positive and negative coupling coefficients, to a static final configuration in which the particles lie equally spaced on $S^{d-1}$. Completely synchronized configurations also exist, but are unstable under the $d$-body interactions. We compare the relative effect of $2$-body and $d$-body forces by adding the well-studied $2$-body interactions to the potential, and find that higher-order interactions enhance the synchronization of the system, specifically, synchronization to a final configuration consisting of equally spaced particles occurs for all $d$-body and $2$-body coupling constants of any sign, unless the attractive $2$-body forces are sufficiently strong relative to the $d$-body forces. In this case the system completely synchronizes as the $2$-body coupling constant increases through a positive critical value, with either a continuous transition for $d=3$, or discontinuously for $d=5$. Synchronization also occurs if the nodes have distributed natural frequencies of oscillation, provided that the frequencies are not too large in amplitude, even in the presence of repulsive 2-body interactions which by themselves would result in asynchronous behaviour.

A Mismatch Between Theory and Practice in the Transition From Home to a Nursing Home: A Scoping Review

The transition from home to a nursing home is a complex process, existing of three transition phases (pre-, mid- and post-transition). It is often fragmented, leading to negative outcomes for older persons and informal caregivers. To prevent these negative outcomes, knowledge of existing transitional care interventions is paramount. Therefore, a scoping review was performed, summarizing current interventions aiming to improve transitional care. The review identified 17 studies, describing eight multi- and five single-component interventions. From the multi-component interventions, seven main components were identified: education, relationships/communication, improving emotional well-being, personalized care, continuity of care, support provision, and ad hoc counseling. This review identified a clear mismatch between theory on optimal transitional care and current transitional care interventions. All interventions focused on either a specific phase or target population throughout the transition process. This inhibits a continuous transition process in which a partnership between all stakeholders involved exists.

Directionality of PYD filament growth determined by the transition of NLRP3 nucleation seeds to ASC elongation

Inflammasomes sense intrinsic and extrinsic danger signals to trigger inflammatory responses and pyroptotic cell death. Homotypic pyrin domain (PYD) interactions of inflammasome forming Nod-like receptors with the adaptor protein ASC mediate oligomerization into helical filamentous assemblies. These supramolecular organizing centers recruit and activate caspase-1, which results in IL-1β family cytokine maturation and pyroptotic cell death. The molecular details of the critical step in signal transduction of inflammasome signaling, however, remain ill-defined. Here, we describe the cryo-EM structure of the human NLRP3 PYD filament at 3.6 Ang resolution. We identify a unique pattern of highly polar interface residues that form the homomeric interactions leading to characteristic filament ends that we designate as A- and B-end, respectively. Coupling a titration polymerization assay to cryo-EM, we demonstrate that the ASC adaptor protein elongation on NLRP3 PYD filament seeds is unidirectional, associating exclusively to the B-end of the NLRP3 filament. Notably, NLRP3 and ASC PYD filaments exhibit the same symmetry in rotation and axial rise per subunit, allowing for a continuous transition between NLRP3 as the nucleation seed and ASC as the elongator. Integrating the directionality of filament growth, we present a molecular model of the ASC speck consisting of active NLRP3-NEK7, ASC, and Caspase-1 proteins.

Explosive synchronization: from synthetic to real-world networks (Interdisciplinary Physics)

Synchronization is a widespread phenomenon in both synthetic and real-world networks. This collective behavior of simple and complex systems has been attracting much research during the last decades. Two different routes to synchrony are defined in networks; first-order, characterized as explosive, and second-order, characterized as continuous transition. Although pioneer researches explained that the transition type is a generic feature in the networks, recent studies proposed some frameworks in which different phase and even chaotic oscillators exhibit explosive synchronization. The relationship between the structural properties of the network and the dynamical features of the oscillators is mainly proclaimed because some of these frameworks show abrupt transitions. Despite different theoretical analyses about the appearance of the first-order transition, studies are limited to the mean-field theory, which cannot be generalized to all networks. There are different real-world and man-made networks whose properties can be characterized in terms of explosive synchronization, e.g., the transition from unconsciousness to wakefulness in the brain and spontaneous synchronization of power-grid networks. In this review article, explosive synchronization is discussed from two main aspects. First, pioneer articles are categorized from the dynamical-structural framework point of view. Then, articles that considered different oscillators in the explosive synchronization frameworks are studied. In this article, the main focus is on the explosive synchronization in networks with chaotic and neuronal oscillators. Also, efforts have been made to consider the recent articles which proposed new frameworks of explosive synchronization.

Discontinuous and continuous transitions of collective behaviors in living systems

Living systems are full of astonishing diversity and complexity of life. Despite differences in the length scales and cognitive abilities of these systems, collective motion of large groups of individuals can emerge. It is of great importance to seek for the fundamental principles of collective motion, such as phase transitions and their natures. Via an eigen microstate approach, we have found a discontinuous transition of density and a continuous transition of velocity in the Vicsek models of collective motion, which are identified by the finite-size scaling form of order-parameter. At strong noise, living systems behave like gas. With the decrease of noise, the interactions between the particles of a living system become stronger and make them come closer. The living system experiences then a discontinuous gas-liquid like transition of density. The even stronger interactions at smaller noise make the velocity directions of particles become ordered and there is a continuous phase transition of collective motion in addition.

Singularity-Free and Cosmologically Viable Born-Infeld Gravity with Scalar Matter

The early cosmology, driven by a single scalar field, both massless and massive, in the context of Eddington-inspired Born-Infeld gravity, is explored. We show the existence of nonsingular solutions of bouncing and loitering type (depending on the sign of the gravitational theory’s parameter, ϵ) replacing the Big Bang singularity, and discuss their properties. In addition, in the massive case, we find some new features of the cosmological evolution depending on the value of the mass parameter, including asymmetries in the expansion/contraction phases, or a continuous transition between a contracting phase to an expanding one via an intermediate loitering phase. We also provide a combined analysis of cosmic chronometers, standard candles, BAO, and CMB data to constrain the model, finding that for roughly |ϵ|≲5·10−8m2 the model is compatible with the latest observations while successfully removing the Big Bang singularity. This bound is several orders of magnitude stronger than the most stringent constraints currently available in the literature.