Crystal structure resolution of two different chlorhexidine salts

This work was partly funded by the British Heart Foundation (NH/11/8/29253) and the EPSRC (EP/K005499/1). CCDC 1416048 and 1416049 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cifTwo salts of the chlorhexidine di-cation (H2CHx2+) – (H2CHx)(SO4)·3H2O and (H2CHx)(CO3)·4H2O – have been synthesised and characterised crystallographically.Publisher PDFPeer reviewe

Synthesis and crystallographic characterisation of Mg(H2dhtp)(H2O)5·H2O

This work was funded by the British Heart Foundation (NH/11/8/29253) and the EPSRC (EP/K005499/1) (EP/K503162/1). CCDC 1432662 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.A mononuclear complex of composition Mg(H2dhtp)(H2O)5·H2O has been prepared and characterised crystallographically.PostprintPostprintPeer reviewe

Effects of Atmospheric CO2 Level on the Metabolic Response of Resistant and Susceptible Wheat to Fusarium graminearum Infection.

Rising atmospheric CO2 concentrations and associated climate changes are thought to have contributed to the steady increase of Fusarium head blight (FHB) on wheat. However, our understanding of precisely how elevated CO2 influences the defense response of wheat against Fusarium graminearum remains limited. In this study, we evaluated the metabolic profiles of susceptible (Norm) and moderately resistant (Alsen) spring wheat in response to whole-head inoculation with two deoxynivalenol (DON)-producing F. graminearum isolates (DON+), isolates 9F1 and Gz3639, and a DON-deficient (DON−) isolate (Gzt40) at ambient (400 ppm) and elevated (800 ppm) CO2 concentrations. The effects of elevated CO2 were dependent on both the Fusarium strain and the wheat variety, but metabolic differences in the host can explain the observed changes in F. graminearum biomass and DON accumulation. The complexity of abiotic and biotic stress interactions makes it difficult to determine if the observed metabolic changes in wheat are a result of CO2-induced changes in the host, the pathogen, or a combination of both. However, the effects of elevated CO2 were not dependent on DON production. Finally, we identified several metabolic biomarkers for wheat that can reliably predict FHB resistance or susceptibility, even as atmospheric CO2 levels rise

Blood levels of lead and dental caries in permanent teeth

ObjectivesThe purpose of this study was to determine whether there is an association between lead exposure within the ages of 1- 4- years and dental caries in the permanent dentition between ages 9- 17 among Mexican youth.MethodsData were collected for the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort from a group of 490 children born and reared in Mexico City. Among ages 1- 4- years, blood lead levels were measured in micrograms of lead per deciliter of blood (μg/dL) and the presence of caries in adolescence was determined using the International Caries and Detection and Assessment System (ICDAS). The relationship between blood levels of lead and decayed, missing, or filled surfaces (DMFS) was examined using negative binomial regression. Covariates were selected based on previous studies and included age, gender, socioeconomic status, oral hygiene, body mass index, and diet. The nonlinear relationship between lead and DMFS was examined using smoothing splines.ResultsThe mean overall blood lead level (BLL) was 4.83- μg/dL (S.D. of 2.2). The mean overall caries level (DMFS) was 4.1. No statistically significant association was found between early childhood blood lead levels and dental caries in adolescence.ConclusionThis study shows a lack of association between exposure to lead between the ages of 1- 4- years of age and dental caries in permanent dentition later in life. Other covariates, such as age and sugar consumption, appeared to play a more prominent role in caries development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163870/1/jphd12384.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163870/2/jphd12384_am.pd

Characterization of a Fusarium graminearum Salicylate Hydroxylase

Salicylic acid (SA) plays an important role in regulating plant defense responses against pathogens. However, pathogens have evolved ways to manipulate plant SA-mediated defense signaling. Fusarium graminearum causes Fusarium head blight (FHB) and reduces crop yields and quality by producing various mycotoxins. In this study, we aimed to identify the salicylate hydroxylase in F. graminearum and determine its role in wheat head blight development. We initially identified a gene in F. graminearum strain NRRL 46422 that encodes a putative salicylate hydroxylase (designated FgShyC). However, the FgShyC deletion mutant showed a similar ability to degrade SA as wild-type strain 46422; nor did overexpression of FgShyC in E. coli convert SA to catechol. The results indicate that FgShyC is not involved in SA degradation. Further genome sequence analyses resulted in the identification of eight salicylate hydroxylase candidates. Upon addition of 1 mM SA, FGSG_03657 (designated FgShy1), was induced approximately 400-fold. Heterologous expression of FgShy1 in E. coli converted SA to catechol, confirming that FgShy1 is a salicylate hydroxylase. Deletion mutants of FgShy1 were greatly impaired but not completely blocked in SA degradation. Expression analyses of infected tissue showed that FgShy1 was induced during infection, but virulence assays revealed that deletion of FgShy1 alone was not sufficient to affect FHB severity. Although the Fgshy1 deletion mutant did not reduce pathogenicity, we cannot rule out that additional salicylate hydroxylases are present in F. graminearum and characterization of these enzymes will be necessary to fully understand the role of SA-degradation in FHB pathogenesis

Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi

[EN] Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (TRI) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in TRI gene duplication and number of TRI loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the TRI cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of TRI cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungiSISG received funding from the Spanish Ministry of Economy and Competitiveness (grant number MINECO-AGL2015-70671-C2-2-R). TL received funding from the National Institute of Agricultural Sciences, Rural Development Administration (grant number PJ00843203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Distribution, Function, and Evolution of a Gene Essential for Trichothecene Toxin Biosynthesis in Trichoderma

[EN] Trichothecenes are terpenoid toxins produced by species in 10 fungal genera, including species of Trichoderma. The trichothecene biosynthetic gene (tri) cluster typically includes the tri5 gene, which encodes a terpene synthase that catalyzes formation of trichodiene, the parent compound of all trichothecenes. The two Trichoderma species, Trichoderma arundinaceum and T. brevicompactum, that have been examined are unique in that tri5 is located outside the tri cluster in a genomic region that does not include other known tri genes. In the current study, analysis of 35 species representing a wide range of the phylogenetic diversity of Trichoderma revealed that 22 species had tri5, but only 13 species had both tri5 and the tri cluster. tri5 was not located in the cluster in any species. Using complementation analysis of a T. arundinaceum tri5 deletion mutant, we demonstrated that some tri5 homologs from species that lack a tri cluster are functional, but others are not. Phylogenetic analyses suggest that Trichoderma tri5 was under positive selection following its divergence from homologs in other fungi but before Trichoderma species began diverging from one another. We propose two models to explain these diverse observations. One model proposes that the location of tri5 outside the tri cluster resulted from loss of tri5 from the cluster in an ancestral species followed by reacquisition via horizontal transfer. The other model proposes that in species that have a functional tri5 but lack the tri cluster, trichodiene production provides a competitive advantage.S

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Outcome of paediatric intensive care survivors

The development of paediatric intensive care has contributed to the improved survival of critically ill children. Physical and psychological sequelae and consequences for quality of life (QoL) in survivors might be significant, as has been determined in adult intensive care unit (ICU) survivors. Awareness of sequelae due to the original illness and its treatment may result in changes in treatment and support during and after the acute phase. To determine the current knowledge on physical and psychological sequelae and the quality of life in survivors of paediatric intensive care, we undertook a computerised comprehensive search of online databases for studies reporting sequelae in survivors of paediatric intensive care. Studies reporting sequelae in paediatric survivors of cardiothoracic surgery and trauma were excluded, as were studies reporting only mortality. All other studies reporting aspects of physical and psychological sequelae were analysed. Twenty-seven studies consisting of 3,444 survivors met the selection criteria. Distinct physical and psychological sequelae in patients have been determined and seemed to interfere with quality of life. Psychological sequelae in parents seem to be common. Small numbers, methodological limitations and quantitative and qualitative heterogeneity hamper the interpretation of data. We conclude that paediatric intensive care survivors and their parents have physical and psychological sequelae affecting quality of life. Further well-designed prospective studies evaluating sequelae of the original illness and its treatment are warranted