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The β-sheet is one of the common protein secondary structures, and the aberrant aggregation of β-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of β-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a β-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (−0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing β-sheet containing molecular entities for various applications.

Cross-strand interactions are important for the stability of β-sheet structures. Accordingly, cross-strand diagonal interactions between glutamate and arginine analogs with varying side-chain lengths were studied in a series of β-hairpin peptides. The peptides were analyzed by homonuclear two-dimensional nuclear magnetic resonance methods. The fraction folded population and folding free energy of the peptides were derived from the chemical shift data. The fraction folded population trends could be rationalized using the strand propensity of the constituting residues, which was not the case for the peptides with lysine analogs, highlighting the difference between the arginine analogs and lysine analogs. Double-mutant cycle analysis was used to derive the diagonal ion-pairing interaction energetics. The most stabilizing diagonal cross-strand interaction was between the shortest residues (i.e., Asp2–Agp9), most likely due to the least side-chain conformational penalty for ion-pair formation. The diagonal interaction energetics in this study involving the arginine analogs appears to be consistent with and extend beyond our understanding of diagonal ion-pairing interactions involving lysine analogs. The results should be useful for designing β-strand-containing molecules to affect biological processes such as amyloid formation and protein-protein interactions.

The front cover provided by the TheoCheM group from Vrije Universiteit Amsterdam shows the four primary interaction components (hydrogen bonding, cross‐terms, base stacking, and solvation) that determine the stability of B‐DNA duplexes. Quantum chemical analyses identify an interplay between the stabilizing hydrogen bonds between nucleotides that drive the formation of the DNA double‐strand, and the destabilizing loss of stacking interactions within individual strands combined with partial desolvation. The sequence‐dependence in the duplex stability originates mainly from the cross‐terms which can be attractive or repulsive. More information on 10 years of ChemistryOpen can be found in the Research Article by Celine Nieuwland et al.

We have quantum chemically analyzed the influence of nucleotide composition and sequence (that is, order) on the stability of double‐stranded B‐DNA triplets in aqueous solution. To this end, we have investigated the structure and bonding of all 32 possible DNA duplexes with Watson–Crick base pairing, using dispersion‐corrected DFT at the BLYP‐D3(BJ)/TZ2P level and COSMO for simulating aqueous solvation. We find enhanced stabilities for duplexes possessing a higher GC base pair content. Our activation strain analyses unexpectedly identify the loss of stacking interactions within individual strands as a destabilizing factor in the duplex formation, in addition to the better‐known effects of partial desolvation. Furthermore, we show that the sequence‐dependent differences in the interaction energy for duplexes of the same overall base pair composition result from the so‐called “diagonal interactions” or “cross terms”. Whether cross terms are stabilizing or destabilizing depends on the nature of the electrostatic interaction between polar functional groups in the pertinent nucleobases. All about that sequence! Quantum chemical analyses reveal that the stability of B‐DNA triplets depends not only on the nucleotide composition, but also on the order in which the nucleotides occur. This sequence dependence in the duplex stability results primarily from attractive or repulsive cross terms between bases in adjacent Watson–Crick pairs.

Acetylcholine (ACh), released in the hippocampus from fibers originating in the medial septum/diagonal band of Broca (MSDB) complex, is crucial for learning and memory. The CA2 region of the hippocampus has received increasing attention in the context of social memory. However, the contribution of ACh to this process remains unclear. Here, we show that in mice, ACh controls social memory. Specifically, MSDB cholinergic neurons inhibition impairs social novelty discrimination, meaning the propensity of a mouse to interact with a novel rather than a familiar conspecific. This effect is mimicked by a selective antagonist of nicotinic AChRs delivered in CA2. Ex vivo recordings from hippocampal slices provide insight into the underlying mechanism, as activation of nAChRs by nicotine increases the excitatory drive to CA2 principal cells via disinhibition. In line with this observation, optogenetic activation of cholinergic neurons in MSDB increases the firing of CA2 principal cells in vivo. These results point to nAChRs as essential players in social novelty discrimination by controlling inhibition in the CA2 region.

Intergenerational social mobility has immense implications for individuals’well-being, attitudes, and behaviors. However, previous methods may be unreliable for estimating heterogeneous mobility effects, especially in the presence of moderate- or large-scale intergenerational mobility. I propose an improved method, called the “mobility contrast model” (MCM). Using simulation evidence, I demonstrate that the MCM is more flexible and reliable for estimating and testing heterogeneous mobility effects, and the results are robust to the scale of intergenerational mobility. I revisit the debate about the effect of mobility on fertility and analyze data from the 1962 Occupational Changes in a Generation Study (OCG-1) and more recent data from the 1974 through 2018 General Social Survey (GSS) using previous models and the MCM. The MCM suggests a small association between fertility and occupational mobility in the GSS data but substantial and heterogeneous educational mobility effects on fertility in the OCG-1 and the GSS. Such effects are difficult to pinpoint using previous methods because mobility effects of different magnitudes and opposite directions among mobility groups may cancel each other out. The new method can be extended to investigate the effect of intergenerational mobility across multiple generations and other research areas, including immigrant assimilation and heterogamy.

Social behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory. Alzheimer’s disease (AD) is mainly characterized by progressive dementia and is accompanied by cognitive impairments, including a decline in social ability. The cholinergic system is a potential constituent for the neural mechanisms underlying social behaviour, and impaired social ability in AD may have a cholinergic basis. However, the involvement of cholinergic function in social behaviour has not yet been fully understood. Here, we performed a selective elimination of cholinergic cell groups in the basal forebrain in mice to examine the role of cholinergic function in social interaction and social recognition memory by using the three-chamber test. Elimination of cholinergic neurons in the medial septum (MS) and vertical diagonal band of Broca (vDB) caused impairment in social interaction, whereas ablating cholinergic neurons in the nucleus basalis magnocellularis (NBM) impaired social recognition memory. These impairments were restored by treatment with cholinesterase inhibitors, leading to cholinergic system activation. Our findings indicate distinct roles of MS/vDB and NBM cholinergic neurons in social interaction and social recognition memory, suggesting that cholinergic dysfunction may explain social ability deficits associated with AD symptoms.

This paper presents an experimental investigation into the structural and material response of ambient-dry and wet clay-brick/lime-mortar masonry elements. In addition to cyclic tests on four large-scale masonry walls subjected to lateral in-plane displacement and co-existing compressive gravity load, the study also includes complementary tests on square masonry panels under diagonal compression and cylindrical masonry cores in compression. After describing the specimen details, wetting method and testing arrangements, the main results and observations are provided and discussed. The results obtained from full-field digital image correlation measurements enable a detailed assessment of the material shear-compression strength envelope, and permit a direct comparison with the strength characteristics of structural walls. The full load-deformation behaviour of the large-scale walls is also evaluated, including their ductility and failure modes, and compared with the predictions of available assessment models. It is shown that moisture has a notable effect on the main material properties, including the shear and compression strengths, brick–mortar interaction parameters, and the elastic and shear moduli. The extent of the moisture effects is a function of the governing behaviour and material characteristics as well as the interaction between shear and precompression stresses, and can lead to a loss of more than a third of the stiffness and strength. For the large scale wall specimens subjected to lateral loading and co-existing compression, the wet-to-dry reduction was found to be up to 20% and 11% in terms of stiffness and lateral strength, respectively, whilst the ductility ratio diminished by up to 12%. Overall, provided that the key moisture-dependent material properties are appropriately evaluated, it is shown that analytical assessment methods can be reliably adapted for predicting the response, in terms of the lateral stiffness, strength and overall load-deformation, for both dry and wet masonry walls.

Data on interdiffusion coefficients in quaternary and higher order systems have been almost absent in the literature due to the scarcity in proper experimental techniques. In the present work, interdiffusion coefficients are reported at 1000 °C in FeNiCoCr and FeNiCoCrMn systems using square root diffusivity analysis of the diffusion couples prepared based on body diagonal diffusion couple approach. Strong diffusional interactions have been manifested in terms of the large values of the cross interdiffusion coefficients compared with the respective main interdiffusion coefficients. D ~ NiCo Cr and D ~ CoNi Cr were both found to be positive and, 54.5-66.7% and 30-50% of the respective main coefficients in the case of quaternary Fe-Ni-Co-Cr system. D ~ FeNi Cr and D ~ FeCo Cr were found to be positive and, 74.5-85.2% and 50.9-59% of the main coefficient D ~ FeFe Cr whereas D ~ NiMn Cr was found to be negative and 57.5-63.6% of the main coefficient D ~ NiNi Cr in magnitude in the case of quinary Fe-Ni-Co-Cr-Mn system. Errors associated with the interdiffusivities determined using the square root diffusivity approach are higher in comparison to the Kirkaldy’s method for quaternary system. However, the trend is reversed for the quinary system. Successful application of the square root diffusivity technique to the body-diagonal diffusion couples prepared in these systems indicate that the interdiffusion coefficients are constant over a large composition range in the two studied systems.

We consider the evolution of an initially localized wave packet after a sudden change in the Hamiltonian, i.e. a quench. When both bound and scattering eigenstates exist in the post-quench Hamiltonian, one might expect partial delocalization of the wave packet to ensue. Here we show that if the quench consists of a sudden switching-off of short-range inter-particle interactions, then Tanʼs universal relations guarantee delocalization through the high-momentum tail of the momentum distribution. Furthermore, we consider the influence of the range of the interaction and show how a finite range alters the coupling to highly excited states. We illustrate our results using numerical simulations of externally trapped particles in one dimension. If the external potential is both disordered and correlated, then the interaction quench leads to transport via delocalized states, showing that localization in disordered systems is sensitive to non-adiabatic changes in the interactions between particles.