Regioselective Synthesis of Indene from 3-Aryl Propargylic gem -Dipivalates Catalyzed by N -Heterocyclic Carbene Gold(I) Complexes

International audience1-Aryl-3,3-bis(pivaloyloxy)propynes can be converted in good to high yields into either 1,3-or 1,2-bis(pivaloyloxy)indenes, depending on the N-heterocyclic carbene (NHC) gold(I) hexafluoroantimonate catalyst used. Almost exclusive formation of 1,3-di(oxycarbonyl)indene derivatives was achieved with cationic gold complexes containing the embracing N,N'-1,3-bis(9-butylfluorenyl)benzimidazolylidene ligand (nBu FNHC). The regioselective issue of the reaction was rationalized by the specific spatial distribution of the steric bulk in the nBu FNHC ligand. In contrast, only modest selectivities in favor of 1,2-disubstituted indenes were observed with more classical NHC gold complexes, the best selectivity being then obtained with N,N'-1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolylidene gold chloride (SIPrAuCl) as precatalyst

Prospectus, April 28, 1969

CAGERS REWARDED AT BANQUET; Dean\u27s Team; Parkland Tops; Black Rap; Readerspeak; Grey Is The Way; BSA; Quote Of The Week; PC Board Elects; Joel Fort; Just Ask Minerva!; Registrations ; Scholarships Available; To Mel; Spring Fine Arts Exhibit; Veterans\u27 Dinner; Auto Farm Equipment Club; Doris Larson Interview; Kenneth Armstrong: South Vietnam, An Endless Circle?; Parkland Honors First Cagers; 2 Cobras Named By Paper; Staerkel Guest Speaker, Eight Letter Winners; IM All-Stars Whip Faculty; Counselors\u27 Corner...; ED. Committee Approves Lawhttps://spark.parkland.edu/prospectus_1969/1008/thumbnail.jp

Findings and Recommendations: ULS FY16 Action on Geospatial Information, Spatial Literacy, Mapping, and GIS

The University Library System (ULS) annual plan for FY16 included the following action and its associated outcomes:  "Action: Supply up­ to­ date geospatial data equipment, data resources, and dedicated staff to provide service across disciplines in the use of geospatial data and to promote the ULS’ role as a campus hub for geospatial data activity and expertise. Outcomes: Identify equipment, software, staffing, and training needs. Purchase equipment and software and hire staff. Develop communications plan. Offer training sessions provided to ULS staff and the university community. Showcase successful projects." To support this action, a project team was chartered and began to work in November, 2015. During the fall of 2015 and the spring of 2016, the project team gathered information, analyzed it, and produced findings and recommendations. This report, which shares those findings and recommendations, represents the main deliverable of the project team

A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development

Background: The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings: Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions: Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection

A Two-Gene Balance Regulates Salmonella Typhimurium Tolerance in the Nematode Caenorhabditis elegans

Lysozymes are antimicrobial enzymes that perform a critical role in resisting infection in a wide-range of eukaryotes. However, using the nematode Caenorhabditis elegans as a model host we now demonstrate that deletion of the protist type lysozyme LYS-7 renders animals susceptible to killing by the fatal fungal human pathogen Cryptococcus neoformans, but, remarkably, enhances tolerance to the enteric bacteria Salmonella Typhimurium. This trade-off in immunological susceptibility in C. elegans is further mediated by the reciprocal activity of lys-7 and the tyrosine kinase abl-1. Together this implies a greater complexity in C. elegans innate immune function than previously thought

Complete Killing of Caenorhabditis elegans by Burkholderia pseudomallei Is Dependent on Prolonged Direct Association with the Viable Pathogen

Background: Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. Much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis. Methodology/Principal Findings: In this study, we showed that different isolates of B. pseudomallei have divergent ability to kill the soil nematode Caenorhabditis elegans. The rate of nematode killing was also dependent on growth media: B. pseudomallei grown on peptone-glucose media killed C. elegans more rapidly than bacteria grown on the nematode growth media. Filter and bacteria cell-free culture filtrate assays demonstrated that the extent of killing observed is significantly less than that observed in the direct killing assay. Additionally, we showed that B. pseudomallei does not persistently accumulate within the C. elegans gut as brief exposure to B. pseudomallei is not sufficient for C. elegans infection. Conclusions/Significance: A combination of genetic and environmental factors affects virulence. In addition, we have also demonstrated that a Burkholderia-specific mechanism mediating the pathogenic effect in C. elegans requires proliferating B

Co-Regulation of the DAF-16 Target Gene, cyp-35B1/dod-13, by HSF-1 in C. elegans Dauer Larvae and daf-2 Insulin Pathway Mutants

Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans

The Roles and Acting Mechanism of Caenorhabditis elegans DNase II Genes in Apoptotic DNA Degradation and Development

DNase II enzymes are acidic endonucleases that have been implicated in mediating apoptotic DNA degradation, a critical cell death execution event. C. elegans genome contains three DNase II homologues, NUC-1, CRN-6, and CRN-7, but their expression patterns, acting sites, and roles in apoptotic DNA degradation and development are unclear. We have conducted a comprehensive analysis of three C. elegans DNase II genes and found that nuc-1 plays a major role, crn-6 plays an auxiliary role, and crn-7 plays a negligible role in resolving 3′ OH DNA breaks generated in apoptotic cells. Promoter swapping experiments suggest that crn-6 but not crn-7 can partially substitute for nuc-1 in mediating apoptotic DNA degradation and both fail to replace nuc-1 in degrading bacterial DNA in intestine. Despite of their restricted and largely non-overlapping expression patterns, both CRN-6 and NUC-1 can mediate apoptotic DNA degradation in many cells, suggesting that they are likely secreted nucleases that are retaken up by other cells to exert DNA degradation functions. Removal or disruption of NUC-1 secretion signal eliminates NUC-1's ability to mediate DNA degradation across its expression border. Furthermore, blocking cell corpse engulfment does not affect apoptotic DNA degradation mediated by nuc-1, suggesting that NUC-1 acts in apoptotic cells rather than in phagocytes to resolve 3′ OH DNA breaks. Our study illustrates how multiple DNase II nucleases play differential roles in apoptotic DNA degradation and development and reveals an unexpected mode of DNase II action in mediating DNA degradation

Diatom-derived oxylipins induce cell death in sea urchin embryos activating caspase-8 and caspase 3/7

Diatoms are an important class of unicellular algae that produce bioactive secondary metabolites withcytotoxic activity collectively termed oxylipins, including polyunsaturated aldehydes (PUAs), hydroxy-acids (HEPEs), oxo-acids and epoxyalcohols. Previous results showed that at higher concentrations, thePUA decadienal induced apoptosis on copepods and sea urchin embryos via caspase-3 activation; atlower concentrations decadienal affected the expression levels of the caspase-8 gene in embryos of thesea urchin Paracentrotus lividus. In the present work, we studied the effects of other common oxylip-ins produced by diatoms: two PUAs (heptadienal and octadienal) and four hydroxyacids (5-, 9- 11- and15-HEPE) on P. lividus cell death and caspase activities. Our results showed that (i) at higher concentra-tions PUAs and HEPEs induced apoptosis in sea urchin embryos, detected by microscopic observationand through the activation of caspase-3/7 and caspase-8 measured by luminescent assays; (ii) at lowconcentrations, PUAs and HEPEs affected the expression levels of caspase-8 and caspase-3/7 (isolated forthe first time here in P. lividus) genes, detected by Real Time qPCR. These findings have interesting impli-cations from the ecological point of view, given the importance of diatom blooms in nutrient-rich aquaticenvironments