Mechanism of Molybdenum-Mediated Carbon Monoxide Deoxygenation and Coupling: Mono- and Dicarbyne Complexes Precede C–O Bond Cleavage and C–C Bond Formation

Deoxygenative coupling of CO to value-added C_(≥2) products is challenging and mechanistically poorly understood. Herein, we report a mechanistic investigation into the reductive coupling of CO, which provides new fundamental insights into a multielectron bond-breaking and bond-making transformation. In our studies, the formation of a bis(siloxycarbyne) complex precedes C–O bond cleavage. At −78 °C, over days, C–C coupling occurs without C–O cleavage. However, upon warming to 0 °C, C–O cleavage is observed from this bis(siloxycarbyne) complex. A siloxycarbyne/CO species undergoes C–O bond cleavage at lower temperatures, indicating that monosilylation, and a more electron-rich Mo center, favors deoxygenative pathways. From the bis(siloxycarbyne), isotopic labeling experiments and kinetics are consistent with a mechanism involving unimolecular silyl loss or C–O cleavage as rate-determining steps toward carbide formation. Reduction of Mo(IV) CO adducts of carbide and silylcarbyne species allowed for the spectroscopic detection of reduced silylcarbyne/CO and mixed silylcarbyne/siloxycarbyne complexes, respectively. Upon warming, both of these silylcarbynes undergo C–C bond formation, releasing silylated C_2O_1 fragments and demonstrating that the multiple bonded terminal Mo≡C moiety is an intermediate on the path to deoxygenated, C–C coupled products. The electronic structures of Mo carbide and carbyne species were investigated quantum mechanically. Overall, the present studies establish the elementary reactions steps by which CO is cleaved and coupled at a single metal site

On the computation of zone and double zone diagrams

Classical objects in computational geometry are defined by explicit relations. Several years ago the pioneering works of T. Asano, J. Matousek and T. Tokuyama introduced "implicit computational geometry", in which the geometric objects are defined by implicit relations involving sets. An important member in this family is called "a zone diagram". The implicit nature of zone diagrams implies, as already observed in the original works, that their computation is a challenging task. In a continuous setting this task has been addressed (briefly) only by these authors in the Euclidean plane with point sites. We discuss the possibility to compute zone diagrams in a wide class of spaces and also shed new light on their computation in the original setting. The class of spaces, which is introduced here, includes, in particular, Euclidean spheres and finite dimensional strictly convex normed spaces. Sites of a general form are allowed and it is shown that a generalization of the iterative method suggested by Asano, Matousek and Tokuyama converges to a double zone diagram, another implicit geometric object whose existence is known in general. Occasionally a zone diagram can be obtained from this procedure. The actual (approximate) computation of the iterations is based on a simple algorithm which enables the approximate computation of Voronoi diagrams in a general setting. Our analysis also yields a few byproducts of independent interest, such as certain topological properties of Voronoi cells (e.g., that in the considered setting their boundaries cannot be "fat").Comment: Very slight improvements (mainly correction of a few typos); add DOI; Ref [51] points to a freely available computer application which implements the algorithms; to appear in Discrete & Computational Geometry (available online

Strategic green infrastructure planning in Germany and the UK: a transnational evaluation of the evolution of urban greening policy and practice

The evolution of Green Infrastructure (GI) planning has varied dramatically between nations. Although a grounded set of principles are recognized globally, there is increasing variance in how these are implemented at a national and sub-national level. To investigate this the following paper presents an evaluation of how green infrastructure has been planned for in England and Germany illustrating how national policy structures facilitate variance in application. Adopting an evaluative framework linked to the identification of GI, its development and monitoring/ feedback the paper questions the impacts on delivery of intersecting factors including terminology, spatial distribution and functionality on effective GI investment. This process reviews how changing policy structures have influenced the framing of green infrastructure policy, and subsequent impact this has on the delivery of green infrastructure projects

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

Sugary interfaces mitigate contact damage where stiff meets soft

The byssal threads of the fan shell Atrina pectinata are non-living functional materials intimately associated with living tissue, which provide an intriguing paradigm of bionic interface for robust load-bearing device. An interfacial load-bearing protein (A. pectinata foot protein-1, apfp-1) with L-3,4-dihydroxyphenylalanine (DOPA)-containing and mannose-binding domains has been characterized from Atrina's foot. apfp-1 was localized at the interface between stiff byssus and the soft tissue by immunochemical staining and confocal Raman imaging, implying that apfp-1 is an interfacial linker between the byssus and soft tissue, that is, the DOPA-containing domain interacts with itself and other byssal proteins via Fe3(+)-DOPA complexes, and the mannose-binding domain interacts with the soft tissue and cell membranes. Both DOPA-and sugar-mediated bindings are reversible and robust under wet conditions. This work shows the combination of DOPA and sugar chemistry at asymmetric interfaces is unprecedented and highly relevant to bionic interface design for tissue engineering and bionic devices

Wiring of Photosystem II to Hydrogenase for Photoelectrochemical Water Splitting.

In natural photosynthesis, light is used for the production of chemical energy carriers to fuel biological activity. The re-engineering of natural photosynthetic pathways can provide inspiration for sustainable fuel production and insights for understanding the process itself. Here, we employ a semiartificial approach to study photobiological water splitting via a pathway unavailable to nature: the direct coupling of the water oxidation enzyme, photosystem II, to the H2 evolving enzyme, hydrogenase. Essential to this approach is the integration of the isolated enzymes into the artificial circuit of a photoelectrochemical cell. We therefore developed a tailor-made hierarchically structured indium-tin oxide electrode that gives rise to the excellent integration of both photosystem II and hydrogenase for performing the anodic and cathodic half-reactions, respectively. When connected together with the aid of an applied bias, the semiartificial cell demonstrated quantitative electron flow from photosystem II to the hydrogenase with the production of H2 and O2 being in the expected two-to-one ratio and a light-to-hydrogen conversion efficiency of 5.4% under low-intensity red-light irradiation. We thereby demonstrate efficient light-driven water splitting using a pathway inaccessible to biology and report on a widely applicable in vitro platform for the controlled coupling of enzymatic redox processes to meaningfully study photocatalytic reactions.This work was supported by the U.K. Engineering and Physical Sciences Research Council (EP/H00338X/2 to E.R. and EP/G037221/1, nanoDTC, to D.M.), the UK Biology and Biotechnological Sciences Research Council (BB/K002627/1 to A.W.R. and BB/K010220/1 to E.R.), a Marie Curie Intra-European Fellowship (PIEF-GA-2013-625034 to C.Y.L), a Marie Curie International Incoming Fellowship (PIIF-GA-2012-328085 RPSII to J.J.Z) and the CEA and the CNRS (to J.C.F.C.). A.W.R. holds a Wolfson Merit Award from the Royal Society.This is the final version of the article. It first appeared from ACS Publications via http://dx.doi.org/10.1021/jacs.5b0373

Selection of antigenically advanced variants of seasonal influenza viruses

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent se

HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages

B lymphopoiesis is the result of several cell-commitment, lineage-choice, and differentiation processes. Every differentiation step is characterized by the activation of a new, lineage-specific, genetic program and the extinction of the previous one. To date, the central role of specific transcription factors in positively regulating these distinct differentiation processes to acquire a B cell-specific genetic program is well established. However, the existence of specific transcriptional repressors responsible for the silencing of lineage inappropriate genes remains elusive. Here we addressed the molecular mechanism behind repression of non-lymphoid genes in B cells. We report that the histone deacetylase HDAC7 was highly expressed in pre-B cells but dramatically down-regulated during cellular lineage conversion to macrophages. Microarray analysis demonstrated that HDAC7 re-expression interfered with the acquisition of the gene transcriptional program characteristic of macrophages during cell transdifferentiation; the presence of HDAC7 blocked the induction of key genes for macrophage function, such as immune, inflammatory, and defense response, cellular response to infections, positive regulation of cytokines production, and phagocytosis. Moreover, re-introduction of HDAC7 suppressed crucial functions of macrophages, such as the ability to phagocytose bacteria and to respond to endotoxin by expressing major pro-inflammatory cytokines. To gain insight into the molecular mechanisms mediating HDAC7 repression in pre-B cells, we undertook co-immunoprecipitation and chromatin immunoprecipitation experimental approaches. We found that HDAC7 specifically interacted with the transcription factor MEF2C in pre-B cells and was recruited to MEF2 binding sites located at the promoters of genes critical for macrophage function. Thus, in B cells HDAC7 is a transcriptional repressor of undesirable genes. Our findings uncover a novel role for HDAC7 in maintaining the identity of a particular cell type by silencing lineage-inappropriate genes

Unguided low intensity cognitive behaviour therapy for anxiety and depression during the COVID-19 pandemic: A randomised trial.

The COVID-19 pandemic has had a severe impact on mental health worldwide, with increased rates of anxiety and depression widely documented. The aim of this study was to examine unguided low intensity cognitive behaviour therapy for anxiety and depression during the pandemic. A sample of 225 individuals in Australia and the United Kingdom (M age 37.79, SD = 14.02, range 18-80 years; 85% female) were randomised into intervention or waitlist control. The intervention group demonstrated significant decreases in anxiety (d = 0.36 [0.18, 0.54]) and depression (d = 0.28 [0.11, 0.45]) compared to controls. The majority of participants (96%) rated the intervention as useful, and most (83%) reported they spent 30 min or less reading the guide, with 83% agreeing the intervention was easy to read. The results indicate that low intensity cognitive behaviour therapy has efficacy in reducing anxiety and depression during the COVID-19 pandemic. There is an urgent need to disseminate low intensity psychological therapies to improve mental health in this challenging time