Nitrogenase-Relevant Reactivity of a Synthetic Iron-Sulfur-Carbon Site.

Simple synthetic compounds with only S and C donors offer a ligation environment similar to the active site of nitrogenase (FeMoco) and thus demonstrate reasonable mechanisms and geometries for N binding and reduction in nature. We recently reported the first example of N binding at a mononuclear iron site supported by only S and C donors. In this work, we report experiments that examine the mechanism of N binding in this system.

Chemical Oxidation of a Coordinated PNP-Pincer Ligand Forms Unexpected Re-Nitroxide Complexes with Reversal of Nitride Reactivity.

Because of the thermodynamic demands of N cleavage, N-derived nitride complexes are often unreactive. The development of multistep N functionalization reactions hinges on methods for modulating nitride reactivity with supporting ligands. Here, we describe the reactions of N-derived Re-nitride complexes, including the first Re nitrides supported by a nitroxide-containing pincer ligand, and unusual examples of Re-nitride complexes.

The impact of perceived workload on nurse satisfaction with work-life balance and intention to leave the occupation.

Background And Aim: In the drive to make the health sector more economically efficient and effective, what is potentially being lost is the need to look after the well-being of those who work within this profession. Nurses are the largest group in the health sector workforce and the frontline of patient care. Workload perceptions are known to be impacting nurses' well-being and are becoming a critical concern for the retention of this workforce.

Of eyes and embryos: subfunctionalization of the CRX homeobox gene in mammalian evolution.

ETCHbox genes are fast-evolving homeobox genes present only in eutherian (placental) mammals which originated by duplication and divergence from a conserved homeobox gene, Cone-rod homeobox (CRX). While expression and function of CRX are restricted to the retina in eutherian mammals, ETCHbox gene expression is specific to preimplantation embryos. This dramatic difference could reflect the acquisition of new functions by duplicated genes or subfunctionalization of pleiotropic roles between CRX and ETCHbox genes.

Gene profiling of head mesoderm in early zebrafish development: insights into the evolution of cranial mesoderm.

Background: The evolution of the head was one of the key events that marked the transition from invertebrates to vertebrates. With the emergence of structures such as eyes and jaws, vertebrates evolved an active and predatory life style and radiated into diversity of large-bodied animals. These organs are moved by cranial muscles that derive embryologically from head mesoderm.

ChIP-exo analysis highlights Fkh1 and Fkh2 transcription factors as hubs that integrate multi-scale networks in budding yeast.

The understanding of the multi-scale nature of molecular networks represents a major challenge. For example, regulation of a timely cell cycle must be coordinated with growth, during which changes in metabolism occur, and integrate information from the extracellular environment, e.g.

A [2Fe-1S] Complex That Affords Access to Bimetallic and Higher-Nuclearity Iron-Sulfur Clusters.

Small, coordinatively unsaturated iron-sulfur clusters are conceived as building blocks for the diverse set of shapes of iron-sulfur clusters in biological and synthetic chemistry. Here we describe a synthetic method for preparing [2Fe-1S] clusters containing two iron(II) ions, which are supported by a relatively unhindered β-diketiminate supporting ligand. The [2Fe-1S] cluster can be isolated in the presence of trimethylphosphine, and the compound with one PMe on each iron(II) ion has been crystallographically characterized.

Dinitrogen Activation and Functionalization using β-Diketiminate Iron Complexes.

Iron catalysts are adept at breaking the N-N bond of N, as exemplified by the iron-catalyzed Haber-Bosch process and the iron-containing clusters at the active sites of nitrogenase enzymes. This Minireview summarizes recent work that has identified a well-characterized set of multi-iron complexes that are capable of breaking and functionalizing N, and are amenable to detailed mechanistic studies. We discuss the redox balancing, the potential intermediates during N activation, the variation of alkali metal reductant, the reversibility of N cleavage, and the formation of N-H and N-C bonds from N.

Dissociating task acquisition from expression during learning reveals latent knowledge.

Performance on cognitive tasks during learning is used to measure knowledge, yet it remains controversial since such testing is susceptible to contextual factors. To what extent does performance during learning depend on the testing context, rather than underlying knowledge? We trained mice, rats and ferrets on a range of tasks to examine how testing context impacts the acquisition of knowledge versus its expression. We interleaved reinforced trials with probe trials in which we omitted reinforcement.

Roles of Iron Complexes in Catalytic Radical Alkene Cross-Coupling: A Computational and Mechanistic Study.

A growing and useful class of alkene coupling reactions involve hydrogen atom transfer (HAT) from a metal-hydride species to an alkene to form a free radical, which is responsible for subsequent bond formation. Here, we use a combination of experimental and computational investigations to map out the mechanistic details of iron-catalyzed reductive alkene cross-coupling, an important representative of the HAT alkene reactions. We are able to explain several observations that were previously mysterious.

Predictive models of eukaryotic transcriptional regulation reveals changes in transcription factor roles and promoter usage between metabolic conditions.

Transcription factors (TF) are central to transcriptional regulation, but they are often studied in relative isolation and without close control of the metabolic state of the cell. Here, we describe genome-wide binding (by ChIP-exo) of 15 yeast TFs in four chemostat conditions that cover a range of metabolic states. We integrate this data with transcriptomics and six additional recently mapped TFs to identify predictive models describing how TFs control gene expression in different metabolic conditions.

The Interaction of Natural Selection and GC Skew May Drive the Fast Evolution of a Sand Rat Homeobox Gene.

Several processes can lead to strong GC skew in localized genomic regions. In most cases, GC skew should not affect conserved amino acids because natural selection will purge deleterious alleles. However, in the gerbil subfamily of rodents, several conserved genes have undergone radical alteration in association with strong GC skew.

Occasion setting.

Occasion setting refers to the ability of 1 stimulus, an occasion setter, to modulate the efficacy of the association between another, conditioned stimulus (CS) and an unconditioned stimulus (US) or reinforcer. Occasion setters and simple CSs are readily distinguished. For example, occasion setters are relatively immune to extinction and counterconditioning, and their combination and transfer functions differ substantially from those of simple CSs.

Reduction of CO by a masked two-coordinate cobalt(i) complex and characterization of a proposed oxodicobalt(ii) intermediate.

Fixation and chemical reduction of CO are important for utilization of this abundant resource, and understanding the detailed mechanism of C-O cleavage is needed for rational development of CO reduction methods. Here, we describe a detailed analysis of the mechanism of the reaction of a masked two-coordinate cobalt(i) complex, L Co (where L = 2,2,6,6-tetramethyl-3,5-bis[(2,6-diisopropylphenyl)imino]hept-4-yl), with CO, which yields two products of C-O cleavage, the cobalt(i) monocarbonyl complex L Co(CO) and the dicobalt(ii) carbonate complex (L Co)(μ-CO). Kinetic studies and computations show that the κ,η-arene isomer of L Co rearranges to the κ , binding mode prior to binding of CO, which contrasts with the mechanism of binding of other substrates to L Co.

HIV risk behaviours among women who inject drugs in coastal Kenya: findings from secondary analysis of qualitative data.

Background: Injecting drug users are at high risk of HIV infection globally. Research related to female drug users is rare in Kenya, yet it is required to inform the development of gender-sensitive HIV prevention and harm reduction services in East Africa, where injecting drug use is on the rise.

Methods: This study aimed to document the nature of HIV risks encountered by women who inject drugs in the Mombasa and Kilifi, Kenya.

Navigating employment retention with a chronic health condition: a meta-ethnography of the employment experiences of people with musculoskeletal disorders in the UK.

Musculoskeletal disorders (MSDs) are associated with high rates of work disability in the UK. This review synthesized qualitative evidence concerning the employment experiences of people with MSDs to explore the factors shaping their employment trajectories post-onset and the resources they draw on to remain in work. Systematic database searches identified 16 qualitative studies of the employment consequences of having a chronic MSD in the UK.

Role of boyfriends and intimate sexual partners in the initiation and maintenance of injecting drug use among women in coastal Kenya.

Introduction: Gender dynamics and interpersonal relations within intimate partnerships are known to determine health behaviors, including substance use, within couples. In addition, influence from intimate partners may occur in the context of wider social ecological determinants of health behavior. The aim of this study was to document the role of intimate partners in influencing injecting drug use among women in Kenya, where injecting drug use is on the rise.

Saccharomyces cerevisiae displays a stable transcription start site landscape in multiple conditions.

One of the fundamental processes that determine cellular fate is regulation of gene transcription. Understanding these regulatory processes is therefore essential for understanding cellular responses to changes in environmental conditions. At the core promoter, the regulatory region containing the transcription start site (TSS), all inputs regulating transcription are integrated.

Amphioxus functional genomics and the origins of vertebrate gene regulation.

Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period.

Isolation and characterization of a high-spin mixed-valent iron dinitrogen complex.

We report a rare example of a mixed-valence iron compound with an FeNNFe core, which gives insight into the structural, spectroscopic, and magnetic influences of single-electron reductions and oxidations. In the new compound, the odd electron is localized as judged from Mössbauer spectra at 80 K and infrared spectra at room temperature, and the backbonding into the N2 unit is intermediate between diiron(i) and diiron(0) congeners. Magnetic susceptibility and relaxation studies on the series of FeNNFe compounds show significant magnetic anisotropy, but through-barrier pathways enable fairly rapid magnetic relaxation.

Divergent influences of the locus coeruleus on migraine pathophysiology.

Migraine is a common disabling neurological condition that is associated with several premonitory symptoms that can occur days before the headache onset. The most commonly reported premonitory symptom is marked fatigue that has been shown to be highly predictive of an ensuing migraine attack. The locus coeruleus (LC) is a key nucleus involved in arousal that has also been shown to impact pain processing.

Equal North: how can we reduce health inequalities in the North of England? A prioritization exercise with researchers, policymakers and practitioners.

Background: The Equal North network was developed to take forward the implications of the Due North report of the Independent Inquiry into Health Equity. The aim of this exercise was to identify how to reduce health inequalities in the north of England.

Methods: Workshops (15 groups) and a Delphi survey (3 rounds, 368 members) were used to consult expert opinion and achieve consensus.

Three-dimensional representation of the many-body quantum state.

Using the trajectory conception of state, we give a simple demonstration that the quantum state of a many-body system may be expressed as a set of states in three-dimensional space, each associated with a different particle. It follows that the many-body wavefunction may be derived from a set of waves in 3-space. Entanglement is represented in the trajectory picture by the mutual dependence of the 3-states on the trajectory labels.