Computational Ligand Descriptors for Catalyst Design

Ligands, especially phosphines and carbenes, can play a key role in modifying and controlling homogeneous organometallic catalysts, and they often provide a convenient approach to fine-tuning the performance of known catalysts. The measurable outcomes of such catalyst modifications (yields, rates, selectivity) can be set into context by establishing their relationship to steric and electronic descriptors of ligand properties, and such models can guide the discovery, optimization, and design of catalysts. In this review we present a survey of calculated ligand descriptors, with a particular focus on homogeneous organometallic catalysis. A range of different approaches to calculating steric and electronic parameters are set out and compared, and we have collected descriptors for a range of representative ligand sets, including 30 monodentate phosphorus­(III) donor ligands, 23 bidentate P,P-donor ligands, and 30 carbenes, with a view to providing a useful resource for analysis to practitioners. In addition, several case studies of applications of such descriptors, covering both maps and models, have been reviewed, illustrating how descriptor-led studies of catalysis can inform experiments and highlighting good practice for model comparison and evaluation

Iron Catalyzed Double Bond Isomerization:Evidence for an FeI/FeIII Catalytic Cycle

Iron‐catalyzed isomerization of alkenes is reported using an iron(II) β‐diketiminate pre‐catalyst. The reaction proceeds with a catalytic amount of a hydride source, such as pinacol borane (HBpin) or ammonia borane (H3N⋅BH3). Reactivity with both allyl arenes and aliphatic alkenes has been studied. The catalytic mechanism was investigated by a variety of means, including deuteration studies, Density Functional Theory (DFT) and Electron Paramagnetic Resonance (EPR) spectroscopy. The data obtained support a pre‐catalyst activation step that gives access to an η2‐coordinated alkene FeI complex, followed by oxidative addition of the alkene to give an FeIII intermediate, which then undergoes reductive elimination to allow release of the isomerization product

Nucleon Magnetic Moments Beyond the Perturbative Chiral Regime

The quark mass dependence of nucleon magnetic moments is explored over a wide range. Quark masses currently accessible to lattice QCD, which lie beyond the regime of chiral perturbation theory (chiPT), are accessed via the cloudy bag model (CBM). The latter reproduces the leading nonanalytic behavior of chiPT, while modeling the internal structure of the hadron under investigation. We find that the predictions of the CBM are succinctly described by the simple formula, \mu_N(m_\pi) = \mu^{(0)}_N / (1 + \alpha m_\pi + \beta m_\pi^2), which reproduces the lattice data, as well as the leading nonanalytic behavior of chiPT. As this form also incorporates the anticipated Dirac moment behavior in the limit m_\pi \to \infty, it constitutes a powerful method for extrapolating lattice results to the physical mass regime.Comment: Revised version accepted for publication includes a new section demonstrating extrapolations of lattice QCD result

Identifying schizophrenia patients who carry pathogenic genetic copy number variants using standard clinical assessment: retrospective cohort study

Background Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia. Aims To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort. Method Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479). Results In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16–34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58–14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28–19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9–86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0–100.0%) for the replication cohort. Conclusions These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders

Regulation of c-Jun NH2-terminal Kinase ( Jnk) Gene Expression during T Cell Activation

The c-Jun NH2-terminal kinases (JNKs) are a group of mitogen-activated protein (MAP) kinases that participate in signal transduction events mediating specific cellular functions. Activation of JNK is regulated by phosphorylation in response to cellular stress and inflammatory cytokines. Here, we demonstrate that JNK is regulated by a second, novel mechanism. Induction of Jnk gene expression is required in specific tissues before activation of this signaling pathway. The in vivo and in vitro ligation of the T cell receptor (TCR) leads to induction of JNK gene and protein expression. TCR signals are sufficient to induce JNK expression, whereas JNK phosphorylation also requires CD28-mediated costimulatory signals. Therefore, both expression and activation contribute to the regulation of the JNK pathway to ensure proper control during the course of an immune response

Evidence for an Association Between Hearing Impairment and Disrupted Sleep: Scoping Review

Purpose: Hearing impairment (HI) is the most common sensory impairment and may negatively impact sleep through reduced auditory input. Factors associated with HI, such as anxiety regarding communication in daily life, may also adversely impact an individual’s sleep. Here, research on the relationship between HI and sleep disruption was catalogued using scoping review methodology. Methods: A systematic strategy was employed to search various electronic databases. This review is reported according to Preferred Reporting Items for Systematic Review and Meta-analysis Scoping Review Extension (PRISMA-ScR). Results: Sixteen records met inclusion criteria. Studies have investigated sleep in HI as a primary aim in noise exposed workers or large surveys in older participants. Experimental and quasi-experimental studies report alterations to sleep architecture of potential neuroplastic origins. Studies reporting sleep as a secondary aim generally report poorer in sleep in HI participants. Conclusions: This scoping review has catalogued evidence that altered or negatively impacted sleep may be associated with HI. Potential confounding factors, mechanisms, and considerations for future research are discussed

Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity

Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits and the corresponding neurophysiological structural and functional alterations are linked to both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. To elucidate the specific role of brain insulin signalling in neuronal functions that are relevant for cognitive processes we have investigated the behaviour of neurons and synaptic plasticity in the hippocampus of mice lacking the insulin receptor substrate protein 2 (IRS-2)