Mononuclear palladium and heterodinuclear palladium–ruthenium complexes of semicarbazone ligands: synthesis, characterization, and application in C–C cross-coupling reactions

Reaction of salicylaldehyde semicarbazone (L-1), 2-hydroxyacetophenone semicarbazone (L-2), and 2-hydroxynaphthaldehyde semicarbazone (L-3) with [Pd(PPh3)(2)Cl-2] in ethanol in the presence of a base (NEt3) affords a family of yellow complexes (1a, 1b and 1c, respectively). In these complexes the semicarbazone ligands are coordinated to palladium in a rather unusual tridentate ONN-mode, and a PPh3 also remains coordinated to the metal center. Crystal structures of the 1b and 1c complexes have been determined, and structure of 1a has been optimized by a DFT method. In these complexes two potential donor sites of the coordinated semicarbazone, viz. the hydrazinic nitrogen and carbonylic oxygen, remain unutilized. Further reaction of these palladium complexes (1a, 1b and 1c) with [Ru(PPh3)(2)(CO)(2)Cl-2] yields a family of orange complexes (2a, 2b and 2c, respectively). In these heterodinuclear (Pd-Ru) complexes, the hydrazinic nitrogen (via dissociation of the N-H proton) and the carbonylic oxygen from the palladium-containing fragment bind to the ruthenium center by displacing a chloride and a carbonyl. Crystal structures of 2a and 2c have been determined, and the structure of 2b has been optimized by a DFT method. All the complexes show characteristic H-1 NMR spectra and, intense absorptions in the visible and ultraviolet region. Cyclic voltammetry on all the complexes shows an irreversible oxidation of the coordinated semicarbazone within 0.86-0.93 V vs. SCE, and an irreversible reduction of the same ligand within -0.96 to -1.14 V vs. SCE. Both the mononuclear (1a, 1b and 1c) and heterodinuclear (2a, 2b and 2c) complexes are found to efficiently catalyze Suzuki, Heck and Sonogashira type C-C coupling reactions utilizing a variety of aryl bromides and aryl chlorides. The Pd-Ru complexes (2a, 2b and 2c) are found to be better catalysts than the Pd complexes (1a, 1b and 1c) for Suzuki and Heck coupling reactions.

Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity. Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals. Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.

Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces

Background: Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development. Results: Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in earlylife environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoorhoused pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results.

Is there sufficient 'sink' in current bioaccessibility determinations of organic pollutants in soils?

Bioaccessibility tests can be used to improve contaminated land risk assessments. For organic pollutants a ‘sink’ is required within these tests to better mimic their desorption under the physiological conditions prevailing in the intestinal tract, where a steep diffusion gradient for the removal of organic pollutants from the soil matrix would exist. This is currently ignored in most PBET systems. By combining the CEPBET bioaccessibility test with an infinite sink, the removal of PAH from spiked solutions was monitored. Less than 10% of spiked PAH remained in the stomach media after 1 h, 10% by 4 h in the small intestine compartment and c.15% after 16 h in the colon. The addition of the infinite sink increased bioaccessibility estimates for field soils by a factor of 1.2–2.8, confirming its importance for robust PBET tests. TOC or BC were not the only factors controlling desorption of the PAH from the soils.

Wearable device to assist independent living

Older people increasingly want to remain living independently in their own homes. The aim of the ENABLE project is to develop a wearable device that can be used to support older people in their daily lives and which can monitor their health status, detect potential problems, provide activity reminders and offer communication and alarm services. In order to determine the specifications and functionality required for the development of the device, user surveys and focus groups were undertaken, use case analysis and scenario modeling carried out. The project has resulted in the development of a wrist-worn device and mobile phone combination that can support and assist older and vulnerable wearers with a range of activities and services both inside their home and as they move around their local environment. The device is currently undergoing pilot trials in five European countries. The aim of this paper is to describe the ENABLE device, its features and services, and the infrastructure within which it operates.

Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism

Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.

Intercomparison of shortwave radiative transfer schemes in global aerosol modeling: results from the AeroCom Radiative Transfer Experiment

In this study we examine the performance of 31 global model radiative transfer schemes in cloud-free conditions with prescribed gaseous absorbers and no aerosols (Rayleigh atmosphere), with prescribed scattering-only aerosols, and with more absorbing aerosols. Results are compared to benchmark results from high-resolution, multi-angular line-by-line radiation models. For purely scattering aerosols, model bias relative to the line-by-line models in the top-of-the atmosphere aerosol radiative forcing ranges from roughly −10 to 20%, with over- and underestimates of radiative cooling at lower and higher solar zenith angle, respectively. Inter-model diversity (relative standard deviation) increases from ~10 to 15% as solar zenith angle decreases. Inter-model diversity in atmospheric and surface forcing decreases with increased aerosol absorption, indicating that the treatment of multiple-scattering is more variable than aerosol absorption in the models considered. Aerosol radiative forcing results from multi-stream models are generally in better agreement with the line-by-line results than the simpler two-stream schemes. Considering radiative fluxes, model performance is generally the same or slightly better than results from previous radiation scheme intercomparisons. However, the inter-model diversity in aerosol radiative forcing remains large, primarily as a result of the treatment of multiple-scattering. Results indicate that global models that estimate aerosol radiative forcing with two-stream radiation schemes may be subject to persistent biases introduced by these schemes, particularly for regional aerosol forcing.