Increased aridity in southwestern Africa during the warmest periods of the last interglacial

Open access journalTerrestrial and marine climatic tracers from marine core MD96-2098 were used to reconstruct glacial-interglacial climate variability in southwestern Africa between 194 and 24 thousand years before present. The pollen record documented three pronounced expansions of Nama-Karoo and fine-leaved savanna during the last interglacial (Marine Isotopic Stage 5 – MIS 5). These Nama-Karoo and fine-leaved savanna expansions were linked to increased aridity during the three warmest substadials of MIS 5. Enhanced aridity potentially resulted from a combination of reduced Benguela Upwelling , expanded subtropical high-pressure cells, and reduced austral-summer precipitation due to a northward shift of the Intertropical Convergence Zone. Decreased austral-winter precipitation was likely linked to a southern displacement of the westerlies. In contrast, during glacial isotopic stages MIS 6, 4 and 3, Fynbos expanded at the expense of Nama-Karoo and fine-leaved savanna indicating a relative increase in precipitation probably concentrated during the austral winter months. Our record also suggested that warm-cold or cold-warm transitions between isotopic stages and substages were punctuated by short increases in humidity. Increased aridity during MIS 5e, 5c and 5a warm substages coincided with minima in both precessional index and global ice volume. On the other hand, austral-winter precipitation increases were associated with precession maxima at the time of well-developed northern-hemisphere ice caps.European Research Counci

Benzo[a]pyrene, Aflatoxine B1 and Acetaldehyde Mutational Patterns in TP53 Gene Using a Functional Assay: Relevance to Human Cancer Aetiology

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B1 exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B1 and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers

Synthesis and biological evaluation of bile carboxamide derivatives with pro-apoptotieffect on human colon adenocarcinoma cell lines.

International audienc

Synthesis and biological evaluation of bile carboxamide derivatives with pro-apoptotieffect on human colon adenocarcinoma cell lines.

International audienc

Mutagenicity of Nitrosubstituted and Amino-substituted Carbazoles In Salmonella-typhimurium .1. Monosubstituted Derivatives of 9h-carbazole

Mononitro, monoamino and monoacetamido carbazoles were assayed for mutagenicity in Salmonella typhimurium strains TA1535, TA1538, TA1537, TA1977, TA98 and TA100, with and without the addition of S9 from phenobarbital-induced rat liver. The role of bacterial metabolism of the nitro group was also studied using the additional strains TA98NR and TA98/1, 8DNP6. None of the compounds was active in TA1535, while only 2-nitrocarbazole and 3-nitrocarbazole presented a weak mutagenicity towards its pKM101 derivative, TA100. All four nitrocarbazole isomers were mutagenic for TA1538 and TA98, their activities decreasing in the order: 2-nitrocarbazole almost-equal-to 3-nitrocarbazole > 1-nitrocarbazole > 4-nitrocarbazole. Direct-acting mutagenicities for TA1537 were lower than for TA1538, but varied in the same order. Nitro reduction was an important step of metabolic activation of nitrocarbazoles, as indicated by the dramatic reduction of activity with TA98NR, as compared to TA98. Results obtained with TA98/1,8DNP6 showed that O-acetyltransferase was only partly required for the expression of mutagenic potency of these compounds. 2-Aminocarbazole was a weak direct-acting mutagen for TA1538 and TA98. Its activity was strongly increased in the presence of S9 mix, while 3-aminocarbazole became active in these conditions. The acetamido derivatives were consistently less mutagenic than their parent amines. These results show that nitrocarbazoles and aminocarbazoles behave as reactive frameshift mutagens, acting mainly through the formation of esterified hydroxylamines. The very low activity of 4-nitrocarbazole might be related to an orientation of the nitro group perpendicular to the aromatic ring