Creation of a functional S-nitrosylation site in vitro by single point mutation

Here we show that in extrahepatic methionine adenosyltransferase replacement of a single amino acid (glycine 120) by cysteine is sufficient to create a functional nitric oxide binding site without affecting the kinetic properties of the enzyme. When wild-type and mutant methionine adenosyltransferase were incubated with S-nitrosoglutathione the activity of the wild-type remained unchanged whereas the activity of the mutant enzyme decreased markedly. The mutant enzyme was found to be S-nitrosylated upon incubation with the nitric oxide donor. Treatment of the S-nitrosylated mutant enzyme with glutathione removed most of the S-nitrosothiol groups and restored the activity to control values. In conclusion, our results suggest that functional S-nitrosylation sites can develop from existing structures without drastic or large-scale amino acid replacement

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age.

The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset - with data collected between 2020 and 2022 - to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

On the rate of black hole binary mergers in galactic nuclei due to dynamical hardening

We assess the contribution of dynamical hardening by direct three-body scattering interactions to the rate of stellar-mass black hole binary (BHB) mergers in galactic nuclei. We derive an analytic model for the single-binary encounter rate in a nucleus with spherical and disc components hosting a super-massive black hole (SMBH). We determine the total number of encounters N-GW needed to harden a BHB to the point that inspiral due to gravitational wave emission occurs before the next three-body scattering event. This is done independently for both the spherical and disc components. Using a Monte Carlo approach, we refine our calculations for NGW to include gravitational wave emission between scattering events. For astrophysically plausible models, we find that typically NGW less than or similar to 10. We find two separate regimes for the efficient dynamical hardening of BHBs: (1) spherical star clusters with high central densities, low-velocity dispersions, and no significant Keplerian component and (2) migration traps in discs around SMBHs lacking any significant spherical stellar component in the vicinity of the migration trap, which is expected due to effective orbital inclination reduction of any spherical population by the disc. We also find a weak correlation between the ratio of the second-order velocity moment to velocity dispersion in galactic nuclei and the rate of BHB mergers, where this ratio is a proxy for the ratio between the rotation-and dispersion-supported components. Because discs enforce planar interactions that are efficient in hardening BHBs, particularly in migration traps, they have high merger rates that can contribute significantly to the rate of BHB mergers detected by the advanced Laser Interferometer Gravitational-Wave Observatory

Using a Software Testing Technique to Improve Theorem Proving

Most efforts to combine formal methods and software testing go in the direction of exploiting formal methods to solve testing problems, most commonly test case generation. Here we take the reverse viewpoint and show how the technique of partition testing can be used to improve a formal proof technique (induction for correctness of loops). We first compute a partition of the domain of the induction variable, based on the branch predicates in the program code of the loop we wish to prove. Based on this partition we derive a partitioned induction rule, which is (hopefully) easier to use than the standard induction rule. In particular, with an induction rule that is tailored to the program to be verified, less user interaction can be expected to be required in the proof. We demonstrate with a number of examples the practical efficiency of our method