Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

*S Supporting Information ABSTRACT: Two nicotinamide adenine dinucleotide (NAD +) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD + (6-N-methyl nicotinamide adenosine 5′-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5′-diphosphoribose, 11), whereas 6-thio NHD + (nicotinamide 6-mercaptopurine 5′-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5′-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5′-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1cIDPR-induced Ca 2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5′-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling

The streamlined genome of Phytomonas spp. relative to human pathogenic kinetoplastids reveals a parasite tailored for plants

Members of the family Trypanosomatidae infect many organisms, including animals, plants and humans. Plant-infecting trypanosomes are grouped under the single genus Phytomonas, failing to reflect the wide biological and pathological diversity of these protists. While some Phytomonas spp. multiply in the latex of plants, or in fruit or seeds without apparent pathogenicity, others colonize the phloem sap and afflict plants of substantial economic value, including the coffee tree, coconut and oil palms. Plant trypanosomes have not been studied extensively at the genome level, a major gap in understanding and controlling pathogenesis. We describe the genome sequences of two plant trypanosomatids, one pathogenic isolate from a Guianan coconut and one non-symptomatic isolate from Euphorbia collected in France. Although these parasites have extremely distinct pathogenic impacts, very few genes are unique to either, with the vast majority of genes shared by both isolates. Significantly, both Phytomonas spp. genomes consist essentially of single copy genes for the bulk of their metabolic enzymes, whereas other trypanosomatids e.g. Leishmania and Trypanosoma possess multiple paralogous genes or families. Indeed, comparison with other trypanosomatid genomes revealed a highly streamlined genome, encoding for a minimized metabolic system while conserving the major pathways, and with retention of a full complement of endomembrane organelles, but with no evidence for functional complexity. Identification of the metabolic genes of Phytomonas provides opportunities for establishing in vitro culturing of these fastidious parasites and new tools for the control of agricultural plant disease. © 2014 Porcel et al

The use of Folsomia candida (Collembola, Isotomidae) in bioassays of waste

Abstract The impacts of cadmium, pentachlorophenol, phenanthrene and of two arti®cially polluted soils, on reproduction by the collembolan Folsomia candida were studied using a test that is in the process of becoming a European standard. The ®rst arti®cially polluted soil was contaminated with metals (cadmium, chromium, lead and zinc), the second with organic chemicals (pentachlorophenol, trichlorophenol and phenanthrene). The EC 50 values for reproduction were 129, 87 and 175 mg/ g, respectively, for cadmium, pentachlorophenol and phenanthrene. Additional experiments dealing with the effects of soil pH and humidity, and of reproduction timing were carried out. A number of problems concerning the experimental conditions and the soil (soil moisture and pH) are discussed. It is concluded than the F. candida reproduction test could be a suitable ecotoxicological test for soil with some technical improvements in relation to organic matter content and test duration, and with more precise speci®cation of the pre-normative ISO guidelines on soil humidity and structure. Further adaptation of the test for soil toxicity evaluation is needed.

Epidemiological study of infantile rotavirus diarrhoea in Tananarive (Madagascar).

International audienceAn epidemiological study of rotavirus infections was conducted in Tananrive, Madagascar, from November 1988 to October 1990. Rotavirus antigen was detected by ELISA in faecal specimens of 183 of 1,659 children with acute diarrhoea (11%) and in 11 of 631 specimens from children without diarrhoea (1.7%). Rotaviral diarrhoeas were most frequently found in infants aged 6 to 18 months and occurred throughout the year with a definite peak during the first winter months. Analysis of the viral RNA by polyacrylamide gel electrophoresis permitted the characterisation of 170 and 194 strains identified. Nine different electropherotypes (A-I) and one mixed infection were observed. The "short" electropherotypes (A-E) were predominant and represented 140 strains (82.4%), and the "long" electropherotypes (F-I and M) represented 30 strains (17.6%). The "short" electropherotype A (cafb) was the most frequent in our environment (45.3% of cases) and was predominant during the first 14 months of the study. The "long" electropherotype F (bbea) appeared in July 1990 and was predominant during the last three months. Among these children with diarrhoea, the presence of rotavirus was significantly associated with vomiting, fever, and moderate to severe dehydration. However, no significant differences in the occurrence of these symptoms were found between the "short" and "long" electropherotypes