Synthesis of Polyhydroxylated Pyrano-Pyrrole Derivatives from Carbohydrate Precursors

The efficient synthesis of novel polyhydroxy‐tetrahydropyrano‐pyrroles from acetylenic carbohydrate precursors in three to four steps is described. The methodology involves, as key steps, the ring contraction of pyridazine intermediates obtained by an inverse‐demand Diels–Alder reaction and subsequent intramolecular lactonization

Review of the Reclamation Techniques for Acid-Generating Mine Wastes upon Closure of Disposal Sites

Acid mine drainage (AMD) remains a major environmental challenge for the mining industry. The preferred options for effectively limiting the environmental impact of AMD consist in controlling the reactions through the use of preventative techniques. Their principal objective is to exclude at least one of the constitutive elements of the chemical reactions, i.e. water, oxygen, or sulfidic minerals. The article recalls the basic principles and reviews different approaches for the prevention and control of AMD upon mine closure. The main methods include multi-layer covers, water covers, and an elevated water table (with a mono-layer cover). Their main advantages, limitations and uncertainties are addressed. Alternative approaches, such as environmental desulphurization and co-disposal of waste rock and tailings, are also discussed

Human immunodeficiency virus type 1 infection of human CD4-transgenic rabbits

International audienc

Positive role of macaque cytotoxic T lymphocytes during SIV infection: decrease of cellular viremia and increase of asymptomatic clinical period.

We have measured cellular viremia and observed clinical outcome of macaques from two cohorts, the first including 12 macaques infected by SIVmac251 and the second including 12 macaques immunized by lipopeptides and then challenged by SIVmac251. In the first cohort (SIV-infected macaques), 3 patterns of CTL responders were determined: high, low and non-responders. In the macaques belonging to pattern of low and non-responders, cellular viremia, measured by growing the virus from PBMC, was continuously high during the first 6 months after infection, and five macaques developed AIDS within 14.4+/-7.7 months. Conversely, in the six high-responder macaques, cellular viremia was constantly low and only one macaque developed AIDS at 19 months, the five others being alive at 24 months. After immunization with lipopeptides, 7/12 macaques showed CTL responses and among these, after SIV challenge, cellular viremia was continually low, and no disease was observed at 22 months of follow-up. Conversely, the five non-responder macaques displayed persistent high viremia and macaques developed AIDS within 12.6+/-2.9 months after SIV challenge. These data strongly suggest that the presence of cytotoxic responses is inversely correlated with cellular viremia and correlated with overall survival and thus is an important component of the immune response in vaccinated individuals. It supports the idea that a strengthening of the CTL responses, if possible, might be beneficial in HIV-infected human beings

Fluorescent labelling of unmodified phosphorothioate oligodeoxynucleotides: Synthesis and characterization

International audienceIn this paper we describe the preparation and characterization of phosphorothioate oligodeoxynucleotides (pt-odn) substituted with a fluorescein molecule linked to the non-bridging sulfur of the internucleotidic linkage. This technique is original in that the starting material is a perphosphorothioate oligonucleotide. The phosphorothioate oligonucleotides, after reaction at pH 8.0 and 50°C with iodoacetamido-fluorescein, yielded a fluorescent derivative, termed F-pt-odn. The two F-pt-odn used in this report contained 1.6 and 3.4 fluorescein per oligonucleotide and were found to be respectively 1.5 and 2.2 times more fluorescent than an alkylamidothiocarbamyl-fluoresceinyl-pt-odn (F-NH-pt-odn) containing a single reporter group. We examined a number of the properties of these oligonucleotides to assess their utility in pharmacokinetic studies. The endocytosis, cellular distribution, and antisense biological activity of these F-pt-odn were similar to those of the starting material (GEM91, complementary to the AUG region of the HIVgag gene) and a F-NH-pt-odn. The F-pt-odn hybridize to their complementary sequence at temperatures up to their Tm of 47.5°C, which is 7°C lower than unmodified GEM91. F-pt-odn are sensitive to alkaline pH and temperature. However, under experimental conditions (pH 7.4) F-pt-odn are more than 70% unchanged after 15 days. After intravenous injection into mice, fluorescent oligonucleotides were easily detectable, in most organs, by HPLC and spectrofluorometry. The tissue distribution of F-pt-odn was found to be similar to that previously reported. We believe that these fluorescent oligonucleotides are of value due to their easy preparation and their high specific fluorescence. In addition, their unaltered cellular uptake and biological activity make them ideal tools for use in pharmacokinetic studies

High Viral Load and CD4 Lymphopenia in Rhesus and Cynomolgus Macaques Infected by a Chimeric Primate Lentivirus Constructed Using theenv, rev, tat,andvpuGenes from HIV-1 Lai

AbstractChimeric primate lentiviruses composed of SIV and HIV genes may allow the analysis of the role of these discrete HIV genes in viral pathogenesis in macaque monkeys. We have constructed a chimeric virus in which theenv, rev, tat,andvpugenes of HIV-1 Lai replace theenv, rev,andtatgenes of the SIVmac239 genome. This virus, SHIVsbg, replicates efficiently in rhesus (Indian and Chinese subspecies) and cynomolgus monkeys with viral loads in PBMC and lymph nodes of up to one infected cell per 30 cells during the acute phase of the infection. Sera from all monkeys recognize specific HIV-1 glycoproteins. The onset of lymphadenopathy in all animals was concurrent with a depletion of CD4 lymphocytes in peripheral blood. The virulence of this SHIV for rhesus and cynomolgus monkeys therefore closely parallels that of HIV-1 for human in the acute phase of the infection. Changes in theenvandvpugenes of a molecular clone of HIV-1 can now be analyzed after passage in nonhuman primate species as the SHIVsbg replicates efficiently. The SHIVsbg-macaque model is an important step in the development of a readily available animal model for HIV-1 vaccine studies