Selective transfers of acetylenic acids to form lecithins

Although acetylenic acids are not normally found in mammalian tissues, octadecynoyl-CoA esters can serve as substrates for rat liver microsomal acyl-CoA: phospholipid acyltransferases. The relatively high rate of transfer to the 2-hydroxyl of 1-acylglycerol-3-phosphorylcholine by the 5-, 9-, and 12-positional cis, trans and yne isomers of acids supports the concept that [pi]-bonds at these positions facilitate esterification irrespective of configuration. The preferred positional isomers for transfer to the 1-hydroxyl, however, are different for the cis and yne derivatives, indicating a sensitivity of the enzyme(s) to configuration. In the latter transfer, an alternating selectivity occurred with the acetylenic isomers between 8 to 13 that was opposite to the pattern for the cis-octadecenoyl transfers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33918/1/0000184.pd

Quantitative effects of unsaturated fatty acids in microbial mutants : VII. Influence of the acetylenic bond location on the effectiveness of acyl chains

The ability of a series of 18 carbon acetylenic fatty acids to fulfill the unsaturated fatty acid requirements of Escherichia coli and Saccharomyces cerevisiae was investigated. Despite their high melting points (>40[deg]C), several isomers of the acetylenic fatty acids were as efficient or more efficient in supporting growth than the analogous fatty acid having a cis-double bond.The efficiencies of the different positional isomers in supporting cell proliferation varied from essentially 0 cells per fmol for the 2-5 and 13-17 isomers to high values when the acetylenic bond was near the center of the chain: e.g. 45 E. coli and 5.5 S. cerevisiae cells/fmol for the 10 isomer. A striking ineffectiveness of the 9 isomer was observed with E. coli. The 7, 8 and 10 isomers were at least 10-fold more efficient than any of the other positional isomers in supporting the growth of E. coli. In contrast, the 9 isomer was among the most effective acetylenic fatty acids tested with the yeast mutant.Chromatographic analysis of the extracted lipids indicated that each of the acetylenic isomers tested (except [Delta]2 and [Delta]3) could be esterified by the prokaryotic and eukaryotic microorganisms. The content of unsaturated plus cyclopropane acids observed when growth ceased in E. coli cultures supplemented with growth-limiting concentrations of the acetylenic fatty acids ranged from approx. 15 mol% for the 8 isomer to approx. 35 mol% for the 14 and 17 isomers. The 8-11 isomers were observed to be esterified predominantly at the two position in phosphatidylethanolamine of E. coli and in phosphatidylcholine of S. cerevisiae.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22954/1/0000521.pd

Expert range maps of global mammal distributions harmonised to three taxonomic authorities

Aim: Comprehensive, global information on species' occurrences is an essential biodiversity variable and central to a range of applications in ecology, evolution, biogeography and conservation. Expert range maps often represent a species' only available distributional information and play an increasing role in conservation assessments and macroecology. We provide global range maps for the native ranges of all extant mammal species harmonised to the taxonomy of the Mammal Diversity Database (MDD) mobilised from two sources, the Handbook of the Mammals of the World (HMW) and the Illustrated Checklist of the Mammals of the World (CMW). Location: Global. Taxon: All extant mammal species. Methods: Range maps were digitally interpreted, georeferenced, error-checked and subsequently taxonomically aligned between the HMW (6253 species), the CMW (6431 species) and the MDD taxonomies (6362 species). Results: Range maps can be evaluated and visualised in an online map browser at Map of Life (mol.org) and accessed for individual or batch download for non-commercial use. Main conclusion: Expert maps of species' global distributions are limited in their spatial detail and temporal specificity, but form a useful basis for broad-scale characterizations and model-based integration with other data. We provide georeferenced range maps for the native ranges of all extant mammal species as shapefiles, with species-level metadata and source information packaged together in geodatabase format. Across the three taxonomic sources our maps entail, there are 1784 taxonomic name differences compared to the maps currently available on the IUCN Red List website. The expert maps provided here are harmonised to the MDD taxonomic authority and linked to a community of online tools that will enable transparent future updates and version control.Fil: Marsh, Charles J.. Yale University; Estados UnidosFil: Sica, Yanina. Yale University; Estados UnidosFil: Burguin, Connor. University of New Mexico; Estados UnidosFil: Dorman, Wendy A.. University of Yale; Estados UnidosFil: Anderson, Robert C.. University of Yale; Estados UnidosFil: del Toro Mijares, Isabel. University of Yale; Estados UnidosFil: Vigneron, Jessica G.. University of Yale; Estados UnidosFil: Barve, Vijay. University Of Florida. Florida Museum Of History; Estados UnidosFil: Dombrowik, Victoria L.. University of Yale; Estados UnidosFil: Duong, Michelle. University of Yale; Estados UnidosFil: Guralnick, Robert. University Of Florida. Florida Museum Of History; Estados UnidosFil: Hart, Julie A.. University of Yale; Estados UnidosFil: Maypole, J. Krish. University of Yale; Estados UnidosFil: McCall, Kira. University of Yale; Estados UnidosFil: Ranipeta, Ajay. University of Yale; Estados UnidosFil: Schuerkmann, Anna. University of Yale; Estados UnidosFil: Torselli, Michael A.. University of Yale; Estados UnidosFil: Lacher, Thomas. Texas A&M University; Estados UnidosFil: Wilson, Don E.. National Museum of Natural History; Estados UnidosFil: Abba, Agustin Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Aguirre, Luis F.. Universidad Mayor de San Simón; BoliviaFil: Arroyo Cabrales, Joaquín. Instituto Nacional de Antropología E Historia, Mexico; MéxicoFil: Astúa, Diego. Universidade Federal de Pernambuco; BrasilFil: Baker, Andrew M.. Queensland University of Technology; Australia. Queensland Museum; AustraliaFil: Braulik, Gill. University of St. Andrews; Reino UnidoFil: Braun, Janet K.. Oklahoma State University; Estados UnidosFil: Brito, Jorge. Instituto Nacional de Biodiversidad; EcuadorFil: Busher, Peter E.. Boston University; Estados UnidosFil: Burneo, Santiago F.. Pontificia Universidad Católica del Ecuador; EcuadorFil: Camacho, M. Alejandra. Pontificia Universidad Católica del Ecuador; EcuadorFil: de Almeida Chiquito, Elisandra. Universidade Federal do Espírito Santo; BrasilFil: Cook, Joseph A.. University of New Mexico; Estados UnidosFil: Cuéllar Soto, Erika. Sultan Qaboos University; OmánFil: Davenport, Tim R. B.. Wildlife Conservation Society; TanzaniaFil: Denys, Christiane. Muséum National d'Histoire Naturelle; FranciaFil: Dickman, Christopher R.. The University Of Sydney; AustraliaFil: Eldridge, Mark D. B.. Australian Museum; AustraliaFil: Fernandez Duque, Eduardo. University of Yale; Estados UnidosFil: Francis, Charles M.. Environment And Climate Change Canada; CanadáFil: Frankham, Greta. Australian Museum; AustraliaFil: Freitas, Thales. Universidade Federal do Rio Grande do Sul; BrasilFil: Friend, J. Anthony. Conservation And Attractions; AustraliaFil: Giannini, Norberto Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Gursky-Doyen, Sharon. Texas A&M University; Estados UnidosFil: Hackländer, Klaus. Universitat Fur Bodenkultur Wien; AustriaFil: Hawkins, Melissa. National Museum of Natural History; Estados UnidosFil: Helgen, Kristofer M.. Australian Museum; AustraliaFil: Heritage, Steven. University of Duke; Estados UnidosFil: Hinckley, Arlo. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Holden, Mary. American Museum of Natural History; Estados UnidosFil: Holekamp, Kay E.. Michigan State University; Estados UnidosFil: Humle, Tatyana. University Of Kent; Reino UnidoFil: Ibáñez Ulargui, Carlos. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Jackson, Stephen M.. Australian Museum; AustraliaFil: Janecka, Mary. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Jenkins, Paula. Natural History Museum; Reino UnidoFil: Juste, Javier. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Leite, Yuri L. R.. Universidade Federal do Espírito Santo; BrasilFil: Novaes, Roberto Leonan M.. Universidade Federal do Rio de Janeiro; BrasilFil: Lim, Burton K.. Royal Ontario Museum; CanadáFil: Maisels, Fiona G.. Wildlife Conservation Society; Estados UnidosFil: Mares, Michael A.. Oklahoma State University; Estados UnidosFil: Marsh, Helene. James Cook University; AustraliaFil: Mattioli, Stefano. Università degli Studi di Siena; ItaliaFil: Morton, F. Blake. University of Hull; Reino UnidoFil: Ojeda, Agustina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Ordóñez Garza, Nicté. Instituto Nacional de Biodiversidad; EcuadorFil: Pardiñas, Ulises Francisco J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Pavan, Mariana. Universidade de Sao Paulo; BrasilFil: Riley, Erin P.. San Diego State University; Estados UnidosFil: Rubenstein, Daniel I.. University of Princeton; Estados UnidosFil: Ruelas, Dennisse. Museo de Historia Natural, Lima; PerúFil: Schai-Braun, Stéphanie. Universitat Fur Bodenkultur Wien; AustriaFil: Schank, Cody J.. University of Texas at Austin; Estados UnidosFil: Shenbrot, Georgy. Ben Gurion University of the Negev; IsraelFil: Solari, Sergio. Universidad de Antioquia; ColombiaFil: Superina, Mariella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Tsang, Susan. American Museum of Natural History; Estados UnidosFil: Van Cakenberghe, Victor. Universiteit Antwerp; BélgicaFil: Veron, Geraldine. Université Pierre et Marie Curie; FranciaFil: Wallis, Janette. Kasokwa-kityedo Forest Project; UgandaFil: Whittaker, Danielle. Michigan State University; Estados UnidosFil: Wells, Rod. Flinders University.; AustraliaFil: Wittemyer, George. State University of Colorado - Fort Collins; Estados UnidosFil: Woinarski, John. Charles Darwin University; AustraliaFil: Upham, Nathan S.. University of Yale; Estados UnidosFil: Jetz, Walter. University of Yale; Estados Unido

Expert range maps of global mammal distributions harmonised to three taxonomic authorities

AimComprehensive, global information on species' occurrences is an essential biodiversity variable and central to a range of applications in ecology, evolution, biogeography and conservation. Expert range maps often represent a species' only available distributional information and play an increasing role in conservation assessments and macroecology. We provide global range maps for the native ranges of all extant mammal species harmonised to the taxonomy of the Mammal Diversity Database (MDD) mobilised from two sources, the Handbook of the Mammals of the World (HMW) and the Illustrated Checklist of the Mammals of the World (CMW).LocationGlobal.TaxonAll extant mammal species.MethodsRange maps were digitally interpreted, georeferenced, error-checked and subsequently taxonomically aligned between the HMW (6253 species), the CMW (6431 species) and the MDD taxonomies (6362 species).ResultsRange maps can be evaluated and visualised in an online map browser at Map of Life (mol.org) and accessed for individual or batch download for non-commercial use.Main conclusionExpert maps of species' global distributions are limited in their spatial detail and temporal specificity, but form a useful basis for broad-scale characterizations and model-based integration with other data. We provide georeferenced range maps for the native ranges of all extant mammal species as shapefiles, with species-level metadata and source information packaged together in geodatabase format. Across the three taxonomic sources our maps entail, there are 1784 taxonomic name differences compared to the maps currently available on the IUCN Red List website. The expert maps provided here are harmonised to the MDD taxonomic authority and linked to a community of online tools that will enable transparent future updates and version control

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers

TPS2646 Background: CD73 expression is elevated in tumors and contributes to increasing levels of immunosuppressive adenosine in the tumor microenvironment. CD73 knockout mice exhibit reduced tumor growth and resistance to experimental metastasis. Inhibition of CD73 activity with an anti-CD73 antibody blocks adenosine production, shown to inhibit tumor growth in syngeneic models. CPI-006 is a humanized IgG1 FcγR binding-deficient anti-CD73 antibody now being investigated in this Phase 1/1b multicenter, open label trial as single agent (SA) or combination with CPI-444, an oral, small molecule, selective A2aR antagonist or in combination with pembrolizumab, an anti-PD1 indicated for the treatment of patients across a number of malignancies (NCT03454451). Methods: Up to 462 subjects will be enrolled at approximately 35 sites in the US, Canada and Australia. Eligible patients must have: non-small cell lung, renal cell carcinoma, urothelial bladder, cervical, colorectal, ovarian, pancreatic, prostate, head and neck, triple-negative breast, endometrial, select sarcomas and non-Hodgkin lymphoma malignancies relapsed, refractory or intolerant to 1 to 5 standard therapies; aged ≥ 18 yo; adequate organ function and measurable disease. The objectives of the study are 1) evaluate the safety and tolerability of SA CPI-006, in combination with CPI-444 and in combination with pembrolizumab, 2) evaluate the pharmacokinetics of each regimen and 3) identify potential biomarker signals predictive of response. Study design in table. Study Design. Clinical trial information: NCT03454451. [Table: see text