Ligand-specific conformational change drives interdomain allostery in Pin1

Pin1 is a two-domain cell regulator that isomerizes peptidyl-prolines. The catalytic domain (PPIase) and the other ligand-binding domain (WW) sample extended and compact conformations. Ligand binding changes the equilibrium of the interdomain conformations, but the conformational changes that lead to the altered domain sampling were unknown. Prior evidence has supported an interdomain allosteric mechanism. We recently introduced a magnetic resonance-based protocol that allowed us to determine the coupling of intra- and interdomain structural sampling in apo Pin1. Here, we describe ligand-specific conformational changes that occur upon binding of pCDC25c and FFpSPR. pCDC25c binding doubles the population of the extended states compared to the virtually identical populations of the apo and FFpSPR-bound forms. pCDC25c binding to the WW domain triggers conformational changes to propagate via the interdomain interface to the catalytic site, while FFpSPR binding displaces a helix in the PPIase that leads to repositioning of the PPIase catalytic loop.

Doublons, topology and interactions in a one-dimensional lattice

We investigate theoretically the Bose–Hubbard version of the celebrated Su-Schrieffer-Heeger topological model, which essentially describes a one-dimensional dimerized array of coupled oscillators with on-site interactions. We study the physics arising from the whole gamut of possible dimerizations of the chain, including both the weakly and the strongly dimerized limiting cases. Focusing on two-excitation subspace, we systematically uncover and characterize the different types of states which may emerge due to the competition between the inter-oscillator couplings, the intrinsic topology of the lattice, and the strength of the on-site interactions. In particular, we discuss the formation of scattering bands full of extended states, bound bands full of two-particle pairs (including so-called ‘doublons’, when the pair occupies the same lattice site), and different flavors of topological edge states. The features we describe may be realized in a plethora of systems, including nanoscale architectures such as photonic cavities, optical lattices and qubits, and provide perspectives for topological two-particle and many-body physics.

Condensates in RNA Repeat Sequences are Heterogeneously Organized and Exhibit Reptation-like Dynamics

Although it is known that RNA undergoes liquid–liquid phase separation (LLPS), the interplay between the molecular driving forces and the emergent features of the condensates, such as their morphologies and dynamical properties, is not well understood. We introduce a coarse-grained model to simulate phase separation of trinucleotide repeat RNAs, which are implicated in neurological disorders such as Huntington disease and amyotrophic lateral sclerosis. After establishing that the simulations reproduce key experimental findings (length and concentration dependence of the phase transition in (CAG)n repeats), we show that once recruited inside the liquid droplets, the monomers transition from hairpin-like structures to extended states. Interactions between the monomers in the condensates result in the formation of an intricate and dense intermolecular network, which severely restrains the fluctuations and mobilities of the RNAs inside large droplets. In the largest densely packed high viscosity droplets, the mobility of RNA chains is best characterized by reptation, reminiscent of the dynamics in polymer melts.

Condensates in RNA Repeat Sequences are Heterogeneously Organized and Exhibit Reptation-like Dynamics

ABSTRACTAlthough it is known that RNA undergoes liquid–liquid phase separation (LLPS), the interplay between the molecular driving forces and the emergent features of the condensates, such as their morphologies and dynamical properties, are not well understood. We develop a coarse-grained model to investigate the phase separation of trinucleotide repeat RNAs, which are implicated in neurological disorders such as Huntington disease and amyotrophic lateral sclerosis. After establishing that the simulations reproduce key experimental findings (length and concentration dependence of the phase transition in (CAG)n repeats), we show that once recruited inside the liquid droplets, the monomers transition from hairpin-like structures to extended states. Interactions between the monomers in the condensates result in the formation of an intricate and dense intermolecular network, which severely restrains the fluctuation and mobility of the RNAs inside large droplets. In the largest densely packed high viscosity droplets, the mobility of RNA chains is best characterized by reptation, reminiscent of the dynamics in polymer melts.

Stereoisomers of Natural Flavonoid Exhibit Different Disruptive Effect and Mechanism of Action on Aβ42 Protofibril

Our simulations reveal that two enantiomeric catechins display a better disruptive effect on Aβ42 protofibril than their stereoisomer epicatechin. Unexpectedly, we find catechins adopt both collapsed and extended states, while...

High-pressure phases of Mn-N system

The highly compressed extended states of light elemental solids have emerged recently as a novel group of energetic materials. However, the application of such materials is seriously limited by the...

Hardware Performance Evaluation of Authenticated Encryption SAEAES with Threshold Implementation

SAEAES is the authenticated encryption algorithm instantiated by combining the SAEB mode of operation with AES, and a candidate of the NIST’s lightweight cryptography competition. Using AES gives the advantage of backward compatibility with the existing accelerators and coprocessors that the industry has invested in so far. Still, the newer lightweight block cipher (e.g., GIFT) outperforms AES in compact implementation, especially with the side-channel attack countermeasure such as threshold implementation. This paper aims to implement the first threshold implementation of SAEAES and evaluate the cost we are trading with the backward compatibility. We design a new circuit architecture using the column-oriented serialization based on the recent 3-share and uniform threshold implementation (TI) of the AES S-box based on the generalized changing of the guards. Our design uses 18,288 GE with AES’s occupation reaching 97% of the total area. Meanwhile, the circuit area is roughly three times the conventional SAEB-GIFT implementation (6229 GE) because of a large memory size needed for the AES’s non-linear key schedule and the extended states for satisfying uniformity in TI.

3× 1018 - 1 × 1019 cm -3 Al+ Ion Implanted 4H-SiC: Annealing Time Effect

This work takes into account low Al implanted concentrations of 3 x 1018 cm-3 and 1 x 1019 cm-3 to compare the results of 1600°C and 1950°C post-implantation annealing treatments, done with two different annealing times per given implanted Al concentration and post implantation annealing temperature. Current-voltage and Hall effect measurements were performed to have the drift hole density and the drift hole mobility curves in the temperature range 100 - 650 K. The fitting of these curves in the frame of a carrier transport into the extended states of the valence band were performed to estimate the Al acceptor density, the donor compensator density, and the Al acceptor ionization energy. Peculiar feature of hole density and hole mobility curves is a contemporaneous increase of both carrier density and mobility values with increasing annealing time, which is congruent with the output parameters of the fitting procedure. The latter shows an almost stable Al electrical activation and a decrease of compensation with increasing annealing time for constant annealing temperature and given implanted Al concentration.