Genetic polymorphism of glutamine synthetase and delta-9 desaturase in families of Pacific oyster Crassostrea gigas and susceptibility to summer mortality

Large-scale mortality events have been observed in Pacific oyster Crassostrea gigas on the west coast of France since the early 1980s, particularly during summer. In order to understand the causes of this mortality, two generations of oysters from single-pair matings were studied in three sites on the French Atlantic coast (Baie-des-Veys, Auray and Ronce-les-Bains). The present paper examines the role of two candidate genes in the susceptibility of oysters to summer mortality, and the selective pressure exerted by such mortality on their polymorphism. Glutamine synthetase (amino-acid metabolism) and delta-9 desaturase (lipid metabolism) genes were studied in the successive generations, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Observed and expected genotypic frequencies were compared. Three different alleles were detected for the glutamine synthetase gene and two for delta-9 desaturase. Allele C of glutamine synthetase seemed to be counter-selected in some second generation families. Allele B of delta-9 desaturase gene was potentially counter-selected at Auray in the families showing higher mortality, and strong selection against BB homozygotes was observed. These observations led us to conclude that any selective effect of summer mortality on allele C of glutamine synthetase gene or allele B of delta-9 desaturase gene could be mediated either directly or via linkage to other loci involved in physiological pathways affecting susceptibility.     

Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate

Axl has been a target of interest in the oncology field for several years based on its role in various oncogenic processes. To date, no wild-type Axl crystal structure has been reported. Herein, we describe the structure-based optimization of a novel chemotype of Axl inhibitors, 1H-imidazole-2-carboxamide, using a mutated kinase homolog, Mer(I650M), as a crystallographic surrogate. Iterative optimization of the initial lead compound (1) led to compound (21), a selective and potent inhibitor of wild-type Axl. Compound (21) will serve as a useful compound for further in vivo studies.     

Dysomma alticorpus,a new species of cutthroat eel from the Gulf of Aqaba,Red Sea (Teleostei: Synaphobranchidae)

The cutthroat eel Dysomma alticorpus n. sp. is described based on a single specimen collected in a trammel net at a depth of 350 m off Eilat, Israel, Gulf of Aqaba, Red Sea. The new species belongs to the Dysomma anguillare species complex, which comprises species possessing a well-developed pectoral fin, intermaxillary teeth, a uniserial row of 7–15 large compound teeth in the lower jaw (which may be followed by a few smaller teeth), and an anteriorly situated anus with the trunk shorter than the head length. It is characterised by a combination of the following characters: origin of the dorsal fin well anterior to the base of the pectoral fin, predorsal length 13.8% TL; preanal length 22.8% TL; three compound teeth on the vomer; head pores: IO 4, SO 3; M 6; POP 0; AD 1, F 0, ST 0; lateral-line pores: predorsal 4, prepectoral 8, preanal 14, total 57–58, the last at the posterior two-thirds of the total length; MVF 7–16–115; total vertebrae 115. Dysomma alticorpus n. sp. is compared with other species of the genus. A revised key to the species of the genera Dysomma and Dysommina is provided.     

On the anatomy and taxonomy of Cerebratulus hepaticus Hubrecht, 1879 (Nemertini) from the Mediterranean (Banyuls-sur-Mer)

The anatomy of an insufficiently described species of heteronemertine, Cerebratulus hepaticus, is redescribed. The species is characterized by, inter alia, a cephalic lacuna with strands of longitudinal muscle fibres, a proboscis with three muscle layers, neurochord cells in the brain, a dermis in the foregut region with no or few longitudinal muscle fibres which is separated from the outer longitudinal muscle layer by connective tissue. The taxon is compared with two other Cerebratulus species, C. fuscus and C. marginatus. The material was collected at Banyuls-sur-Mer (France) in the Mediterranean.     

Spp1 at the crossroads of H3K4me3 regulation and meiotic recombination

In Saccharomyces cerevisiae, all H3K4 methylation is performed by a single Set1 Complex (Set1C) that is composed of the catalytic (Set1) and seven other subunits (Swd1, Swd2, Swd3, Bre2, Sdc1, Spp1 and Shg1). It has been known for quite some time that trimethylated H3K4 (H3K4me3) is enriched in the vicinity of meiotic double-strand breaks (DSBs), but the link between H3K4me3 and the meiotic nuclease Spo11 was uncovered only recently. The PHD-containing subunit Spp1, by interacting with H3K4me3 and Mer2, was shown to promote the recruitment of potential meiotic DSB sites to the chromosomal axis allowing their subsequent cleavage by Spo11. Therefore, Spp1 emerged as a key regulator of the H3K4 trimethylation catalyzed by Set1C and of the formation of meiotic DSBs. These findings illustrate the remarkable multifunctionality of Spp1, which not only regulates the catalytic activity of the enzyme (Set1), but also interacts with the deposited mark, and mediates its biological effect (meiotic DSB formation) independently of the complex. As it was previously described for Swd2, and now for Spp1, we anticipate that other Set1C subunits, in addition to regulating H3K4 methylation, may participate in diverse biological functions inside or outside of the complex.     

Synthesis,biological evaluation,and physicochemical property assessment of 4-substituted 2-phenylaminoquinazolines as Mer tyrosine kinase inhibitors

Current results identified 4-substituted 2-phenylaminoquinazoline compounds as novel Mer tyrosine kinase (Mer TK) inhibitors with a new scaffold. Twenty-one 2,4-disubstituted quinazolines (series 4–7) were designed, synthesized, and evaluated against Mer TK and a panel of human tumor cell lines aimed at exploring new Mer TK inhibitors as novel potential antitumor agents. A new lead, 4b, was discovered with a good balance between high potency (IC₅₀ 0.68 μM) in the Mer TK assay and antiproliferative activity against MV4-11 (GI₅₀ 8.54 μM), as well as other human tumor cell lines (GI₅₀ < 20 μM), and a desirable druglike property profile with low log P value (2.54) and high aqueous solubility (95.6 μg/mL). Molecular modeling elucidated an expected binding mode of 4b with Mer TK and necessary interactions between them, thus supporting the hypothesis that Mer TK might be a biologic target of this kind of new active compound.     

Histoire plio-pléistocène des écosystèmes végétaux de Méditerranée sud-occidentale : apport de l’analyse pollinique de deux sondages en mer d’Alboran

The pollen analysis of sediments of two boreholes located in the northeastern Morocco (Nador 1) and in the southeastern Spain (Andalucia G1) has allowed shedding a new light on the vegetation and climate of the North African littoral plains, the Rif Massif and the Betic Range during the Pliocene. The vegetation around the Alboran Sea was open and xeric during the Zanclean, dominated by herbs including subdesertic elements as Calligonum, Lygeum, Nitraria and Neurada. This type of vegetation indicates a dry and hot climate. The southwestern Mediterranean steppes have therefore a climatic character; they existed before the presence and the heavy pressure of Man on the environment. From the Piacenzian, the development, at Andalucia as well as at Nador, of Artemisia and the appearance of some altitude trees such as Cedrus and Cathaya indicate a vegetation change linked to a climatic change. Modifications in the vegetation observed during the same period in northwestern Mediterranean seem to indicate that the vegetation changes observed at Andalucia and Nador are controlled by the appearance of the first arctic glacial-interglacial cycles. The cedar tree appears at Nador only at the end of the Piacenzian, at time of the first cooling, while it has been found punctually in Messinian and early Pliocene sediments of Habibas in Algeria and in Messinian sediments of the Bou Regreg section at Salé in Morocco. The regular presence of Cedar at Bou Regreg during the Messinian, allows supposing that it was present in the Middle Atlas Mountains and that its development was favoured by colder conditions.     

Some aspects of the Upper Palaeolithic period in Sindh,Pakistan

The study of the Upper Palaeolithic of Sindh is still in its infancy. Although it has slightly improved during the last twenty years, and a few more sites have been discovered in different parts of the province, we are still far from achieving a good knowledge of the sequence of the events that took place during the final stages of the Pleistocene in this region of the Indian Subcontinent. Despite the archaeological importance of the southern part of the country, the Arabian Sea coast in particular, which represents the suggested route followed by Modern Humans to move to India and farther east, most of this territory has not yielded any tangible trace of their passage. The scope of this paper is to update the evidence available for the Upper Palaeolithic of Sindh, and to discuss it within the general framework of the Upper Palaeolithic period of the Indian Subcontinent.