Extending motifs in lithiocuprate chemistry: unexpected structural diversity in thiocyanate complexes.

The new area of lithio(thiocyanato)cuprates has been developed. Using inexpensive, stable and safe CuSCN for their preparation, these complexes revealed Lipshutz-type dimeric motifs with solvent-dependent point group identities; planar, boat-shaped and chair shaped conformers are seen in the solid state. In solution, both Lipshutz-type and Gilman structures are clearly seen. Since the advent in 2007 of directed ortho cupration, effort has gone into understanding the structure-reactivity effects of amide ligand variation in and alkali metal salt abstraction from Lipshutz-type cuprates such as (TMP)2Cu(CN)Li2(THF) 1 (TMP = 2,2,6,6-tetramethylpiperidide). The replacement of CN(-) with SCN(-) is investigated presently as a means of improving the safety of lithium cuprates. The synthesis and solid state structural characterization of reference cuprate (TMP)2Cu(CN)Li2(THP) 8 (THP = tetrahydropyran) precedes that of the thiocyanate series (TMP)2Cu(SCN)Li2(L) (L = OEt29, THF 10, THP 11). For each of 9-11, preformed TMPLi was combined with CuSCN (2 : 1) in the presence of sub-stoichiometric Lewis base (0.5 eq. wrt Li). The avoidance of Lewis basic solvents incurs formation of the unsolvated Gilman cuprate (TMP)2CuLi 12, whilst multidimensional NMR spectroscopy has evidenced the abstraction of LiSCN from 9-11 in hydrocarbon solution and the in situ formation of Gilman reagents. The synthetic utility of 10 is established in the selective deprotometalation of chloropyridine substrates, including effecting transition metal-free homocoupling in 51-69% yield.This work was supported by the U.K. EPSRC through grant EP/J500380/1 (A. P.) and the Ministère de l'Enseignement Supérieur et de la Recherche scientifique Algérien (M. H.). F. M.This is the final version of the article. It was first available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5DT03882

An examination of the precipitation delivery mechanisms for Dolleman Island, eastern Antarctic Peninsula

Copyright @ 2004 Wiley-BlackwellThe variability of size and source of significant precipitation events were studied at an Antarctic ice core drilling site: Dolleman Island (DI), located on the eastern coast of the Antarctic Peninsula. Significant precipitation events that occur at DI were temporally located in the European Centre for Medium-Range Weather Forecasting (ECMWF) reanalysis data set, ERA-40. The annual and summer precipitation totals from ERA-40 at DI both show significant increases over the reanalysis period. Three-dimensional backwards air parcel trajectories were then run for 5 d using the ECMWF ERA-15 wind fields. Cluster analyses were performed on two sets of these backwards trajectories: all days in the range 1979–1992 (the climatological time-scale) and a subset of days when a significant precipitation event occurred. The principal air mass sources and delivery mechanisms were found to be the Weddell Sea via lee cyclogenesis, the South Atlantic when there was a weak circumpolar trough (CPT) and the South Pacific when the CPT was deep. The occurrence of precipitation bearing air masses arriving via a strong CPT was found to have a significant correlation with the southern annular mode (SAM); however, the arrival of air masses from the same region over the climatological time-scale showed no such correlation. Despite the dominance in both groups of back trajectories of the westerly circulation around Antarctica, some other key patterns were identified. Most notably there was a higher frequency of lee cyclogenesis events in the significant precipitation trajectories compared to the climatological time-scale. There was also a tendency for precipitation trajectories to come from more northerly latitudes, mostly from 50–70°S. The El Niño Southern Oscillation (ENSO) was found to have a strong influence on the mechanism by which the precipitation was delivered; the frequency of occurrence of precipitation from the east (west) of DI increased during El Niño (La Niña) events

Estimating viral prevalence with data fusion for adaptive two-phase pooled sampling.

The COVID-19 pandemic has highlighted the importance of efficient sampling strategies and statistical methods for monitoring infection prevalence, both in humans and in reservoir hosts. Pooled testing can be an efficient tool for learning pathogen prevalence in a population. Typically, pooled testing requires a second-phase retesting procedure to identify infected individuals, but when the goal is solely to learn prevalence in a population, such as a reservoir host, there are more efficient methods for allocating the second-phase samples.To estimate pathogen prevalence in a population, this manuscript presents an approach for data fusion with two-phased testing of pooled samples that allows more efficient estimation of prevalence with less samples than traditional methods. The first phase uses pooled samples to estimate the population prevalence and inform efficient strategies for the second phase. To combine information from both phases, we introduce a Bayesian data fusion procedure that combines pooled samples with individual samples for joint inferences about the population prevalence.Data fusion procedures result in more efficient estimation of prevalence than traditional procedures that only use individual samples or a single phase of pooled sampling.The manuscript presents guidance on implementing the first-phase and second-phase sampling plans using data fusion. Such methods can be used to assess the risk of pathogen spillover from reservoir hosts to humans, or to track pathogens such as SARS-CoV-2 in populations

Selective lability of ruthenium(II) arene amino acid complexes.

A series of organometallic complexes of the form [(PhH)Ru(amino acid)](+) have been synthesized using amino acids able to act as tridentate ligands. The straightforward syntheses gave enantiomerically pure complexes with two stereogenic centers due to the enantiopurity of the chelating ligands. Complexes were characterized in the solid-state and/or solution-state where the stability of the complex allowed. The propensity toward labilization of the coordinatively saturated complexes was investigated. The links between complex stability and structural features are very subtle. Nonetheless, H/D exchange rates of coordinated amino groups reveal more significant differences in reactivity linked to metallocycle ring size resulting in decreasing stability of the metallocycle as the amino acid side-chain length increases. The behavior of these systems in acid is unusual, apparently labilizing the carboxylate residue of the amino acid. This acid-catalyzed hemilability in an organometallic is relevant to the use of Ru(II) arenes in medicinal contexts due to the relatively low pH of cancerous cells.TGS and MO thank the EPSRC for Studentships EP/P505445/1 and EP/K503/009/1, respectively.This is the final version of the article. It was first published by ACS at http://pubs.acs.org/doi/abs/10.1021/ic502051

Disentangling serology to elucidate henipa- and filovirus transmission in Madagascar fruit bats.

Bats are reservoirs for emerging human pathogens, including Hendra and Nipah henipaviruses and Ebola and Marburg filoviruses. These viruses demonstrate predictable patterns in seasonality and age structure across multiple systems; previous work suggests that they may circulate in Madagascar's endemic fruit bats, which are widely consumed as human food. We aimed to (a) document the extent of henipa- and filovirus exposure among Malagasy fruit bats, (b) explore seasonality in seroprevalence and serostatus in these bat populations and (c) compare mechanistic hypotheses for possible transmission dynamics underlying these data. To this end, we amassed and analysed a unique dataset documenting longitudinal serological henipa- and filovirus dynamics in three Madagascar fruit bat species. We uncovered serological evidence of exposure to Hendra-/Nipah-related henipaviruses in Eidolon dupreanum, Pteropus rufus and Rousettus madagascariensis, to Cedar-related henipaviruses in E. dupreanum and R. madagascariensis and to Ebola-related filoviruses in P. rufus and R. madagascariensis. We demonstrated significant seasonality in population-level seroprevalence and individual serostatus for multiple viruses across these species, linked to the female reproductive calendar. An age-structured subset of the data highlighted evidence of waning maternal antibodies in neonates, increasing seroprevalence in young and decreasing seroprevalence late in life. Comparison of mechanistic epidemiological models fit to these data offered support for transmission hypotheses permitting waning antibodies but retained immunity in adult-age bats. Our findings suggest that bats may seasonally modulate mechanisms of pathogen control, with consequences for population-level transmission. Additionally, we narrow the field of candidate transmission hypotheses by which bats are presumed to host and transmit potentially zoonotic viruses globally.National Geographic Society (Young Explorer’s and Waitt grants to CEB) PIVOT (research grant to CEB) National Science Foundation (Dissertation Improvement Grant and Graduate Research Fellowship to CEB) Princeton University (Walbridge Research Fund Grant to CEB; Center for Health and Well-being Grant to CJM) a Biological Defense Research Directorate of the Naval Medical Research Center and the Department of Health and Human Services, National Institutes of Health (research grant AI054715 to CCB) Queensland Government Accelerate Postdoctoral Research Fellowship to AJP The Alborada Trust (JLNW

Support for viral persistence in bats from age-specific serology and models of maternal immunity.

Spatiotemporally-localised prediction of virus emergence from wildlife requires focused studies on the ecology and immunology of reservoir hosts in their native habitat. Reliable predictions from mathematical models remain difficult in most systems due to a dearth of appropriate empirical data. Our goal was to study the circulation and immune dynamics of zoonotic viruses in bat populations and investigate the effects of maternally-derived and acquired immunity on viral persistence. Using rare age-specific serological data from wild-caught Eidolon helvum fruit bats as a case study, we estimated viral transmission parameters for a stochastic infection model. We estimated mean durations of around 6 months for maternally-derived immunity to Lagos bat virus and African henipavirus, whereas acquired immunity was long-lasting (Lagos bat virus: mean 12 years, henipavirus: mean 4 years). In the presence of a seasonal birth pulse, the effect of maternally-derived immunity on virus persistence within modelled bat populations was highly dependent on transmission characteristics. To explain previous reports of viral persistence within small natural and captive E. helvum populations, we hypothesise that some bats must experience prolonged infectious periods or within-host latency. By further elucidating plausible mechanisms of virus persistence in bat populations, we contribute to guidance of future field studies

Bat trait, genetic and pathogen data from large-scale investigations of African fruit bats, Eidolon helvum.

Bats, including African straw-coloured fruit bats (Eidolon helvum), have been highlighted as reservoirs of many recently emerged zoonotic viruses. This common, widespread and ecologically important species was the focus of longitudinal and continent-wide studies of the epidemiological and ecology of Lagos bat virus, henipaviruses and Achimota viruses. Here we present a spatial, morphological, demographic, genetic and serological dataset encompassing 2827 bats from nine countries over an 8-year period. Genetic data comprises cytochrome b mitochondrial sequences (n=608) and microsatellite genotypes from 18 loci (n=544). Tooth-cementum analyses (n=316) allowed derivation of rare age-specific serologic data for a lyssavirus, a henipavirus and two rubulaviruses. This dataset contributes a substantial volume of data on the ecology of E. helvum and its viruses and will be valuable for a wide range of studies, including viral transmission dynamic modelling in age-structured populations, investigation of seasonal reproductive asynchrony in wide-ranging species, ecological niche modelling, inference of island colonisation history, exploration of relationships between island and body size, and various spatial analyses of demographic, morphometric or serological data.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/sdata.2016.4

Structural effects in lithiocuprate chemistry:the elucidation of reactive pentametallic complexes

TMPLi (TMP=2,2,6,6-tetramethylpiperidide) reacts with Cu(I) salts in the presence of Et(2)O to give the dimers [{(TMP)(2)Cu(X)Li(2)(OEt(2))}(2)] (X=CN, halide). In contrast, the use of DMPLi (DMP=cis-2,6-dimethylpiperidide) gives an unprecedented structural motif; [{(DMP)(2)CuLi(OEt(2))}(2)LiX] (X=halide). This formulation suggests a hitherto unexplored route to the in situ formation of Gilman-type bases that are of proven reactivity in directed ortho cupration

The role of measuring exhaled breath biomarkers in sarcoidosis: A systematic review

Introduction: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment. Objectives: We undertook a systematic review and meta-analysis, to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non-breath based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment. Methods: Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis. Results: 353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I2 of 93.4% (p<0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment. Conclusions: The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role

Volatile organic compounds associated with diagnosis and disease characteristics in asthma – A systematic review

Background: Metabolomics refers to study of the metabolome, the entire set of metabolites produced by a biological system. The application of metabolomics to exhaled breath samples - breathomics - is a rapidly growing field with potential application to asthma diagnosis and management. Objectives: We aimed to review the adult asthma breathomic literature and present a comprehensive list of volatile organic compounds identified by asthma breathomic models. Methods: We undertook a systematic search for literature on exhaled volatile organic compounds in adult asthma. We assessed the quality of studies and performed a qualitative synthesis. Results: We identified twenty studies; these were methodologically heterogenous with a variable risk of bias. Studies almost universally reported breathomics to be capable of differentiating - with moderate or greater accuracy - between samples from healthy controls and those with asthma; and to be capable of phenotyping disease. However, there was little concordance in the compounds upon which discriminatory models were based. Conclusion: Results to-date are promising but validation in independent prospective cohorts is needed. This may be challenging given the high levels of inter-individual variation. However, large-scale, multi-centre studies are underway and validation efforts have been aided by the publication of technical standards likely to increase inter-study comparability. Successful validation of breathomic models for diagnosis and phenotyping would constitute an important step towards personalised medicine in asthma