Taphonomy and palaeoecology of the late Pleistocene to middle Holocene small mammal succession of El Harhoura 2 cave (Rabat-Témara, Morocco)

The relationship between local and global climatic variations and the origin and dispersal of Homo sapiens in Africa is complex, and North Africa may have played a major role in these events. In Morocco, very few studies are specifically dedicated to small fossil vertebrates, and neither taphonomic nor palaeoecological studies have been undertaken on these taxa, particularly in archaeological contexts. The late Pleistocene to middle Holocene succession of El Harhoura 2 cave, situated in the region of Témara, yields an exceptionally rich small vertebrate assemblage. We present the results of a first systematic, taphonomic, and palaeoecological study of the small mammals from Levels 1 to 8 of El Harhoura 2. The absence of bone sorting and polishing, as well as the presence of significant traces of digestion indicate that the small mammal bones were accumulated in the cave by predators and that no water transport occurred. Other traces observed on the surface of bones consist mainly of root marks and black traces (micro-organisms or more probably manganese) which affected the majority of the material. The percentage of fragmentation is very high in all stratigraphic levels, and the post-depositional breakage (geologic and anthropogenic phenomena) obscure the original breakage patterns of bones by predators. According to the ecology of the different species present in the levels of El Harhoura 2, and by taking into account possible biases highlighted by the taphonomic analysis, we reconstruct the palaeoenvironmental evolution in the region. For quantitative reconstructions we used two indices: the Taxonomic Habitat Index (THI) and the Gerbillinae/Murinae ratio. Late Pleistocene accumulations were characterised by a succession of humid (Levels 3, 4a, 6, and 8) and arid (Levels 2?, 5, and 7) periods, with more or less open landscapes, ending in an ultimate humid and wooded period during the middle Holocene (Level 1). We discuss particular limits of our results and interpretations, due to an important lack of taxonomic, ecological, and taphonomic knowledge in North Africa.     

Larval and juvenile Pacific herring Clupea pallasii are not susceptible to infectious hematopoietic necrosis under laboratory conditions

Infectious hematopoietic necrosis (IHN) leads to periodic epidemics among certain wild and farmed fish species of the Northeast (NE) Pacific. The source of the IHN virus (IHNV) that initiates these outbreaks remains unknown; however, a leading hypothesis involves viral persistence in marine host species such as Pacific herring Clupea pallasii. Under laboratory conditions we exposed specific pathogen-free (SPF) larval and juvenile Pacific herring to 10(3) to 10(4) plaque-forming units (pfu) of IHNV ml(-1) by waterborne immersion. Cumulative mortalities among exposed groups were not significantly different from those of negative control groups. After waterborne exposure, IHNV was transiently recovered from the tissues of larvae but absent in tissues of juveniles. Additionally, no evidence of viral shedding was detected in the tank water containing exposed juveniles. After intraperitoneal (IP) injection of IHNV in juvenile herring with 10(3) pfu, IHNV was recovered from the tissues of sub-sampled individuals for only the first 5 d post-exposure. The lack of susceptibility to overt disease and transient levels of IHNV in the tissues of exposed fish indicate that Pacific herring do not likely serve a major epizootiological role in perpetuation of IHNV among free-ranging sockeye salmon Oncorhynchus nerka and farmed Atlantic salmon Salmo salar in the NE Pacific.     

In vivo fitness associated with high virulence in a vertebrate virus is a complex trait regulated by host entry, replication, and shedding

The relationship between pathogen fitness and virulence is typically examined by quantifying only one or two pathogen fitness traits. More specifically, it is regularly assumed that within-host replication, as a precursor to transmission, is the driving force behind virulence. In reality, many traits contribute to pathogen fitness, and each trait could drive the evolution of virulence in different ways. Here, we independently quantified four viral infection cycle traits, namely, host entry, within-host replication, within-host coinfection fitness, and shedding, in vivo, in the vertebrate virus Infectious hematopoietic necrosis virus (IHNV). We examined how each of these stages of the viral infection cycle contributes to the fitness of IHNV genotypes that differ in virulence in rainbow trout. This enabled us to determine how infection cycle fitness traits are independently associated with virulence. We found that viral fitness was independently regulated by each of the traits examined, with the largest impact on fitness being provided by within-host replication. Furthermore, the more virulent of the two genotypes of IHNV we used had advantages in all of the traits quantified. Our results are thus congruent with the assumption that virulence and within-host replication are correlated but suggest that infection cycle fitness is complex and that replication is not the only trait associated with virulence.     

Synthesis and SAR of 3- and 4-substituted quinolin-2-ones: discovery of mixed 5-HT(1B)/5-HT(2A) receptor antagonists

Quinolin-2-ones bearing a heteroaryl-piperazine linked by a two carbon chain at the 3- or 4-position were synthesised and evaluated as mixed 5-HT(1B)/5-HT(2A) receptor antagonists. Potent mixed antagonists were obtained with thieno[3,2-c]pyridine derivatives. In this series, compound 2.1 (SL 65.0472) proved to be functional antagonist at both the 5-HT(2A) receptor (rat in vivo 5-HT-induced hypertension model) and the 5-HT(1B) receptor (dog in vitro saphenous vein assay).     

Molecular docking of heparin oligosaccharides with Hep-II heparin-binding domain of fibronectin reveals an interplay between the different positions of sulfate groups

Fibronectin is a major component of the extracellular matrix and serves as support for cell adhesion and migration. Heparin and heparan sulfates (HS) have been reported to be high-affinity ligands for fibronectin. The strongest heparin/HS-binding site, named Hep-II, is located in the C-terminal repeat units FN12-14 of fibronectin. Mutational studies of recombinant fibronectin fragments and elucidation of the X-ray crystallographic structure of Hep-II in complex with heparin allowed localizing the main heparin/HS-binding site in FN13 to two parallel amino acid clusters: R1697, R1698, R1700 and R1714, R1716, R1745. Heparin, which is more sulfated than HS, is a better ligand for fibronectin, indicating that the sulfate density is important for the interactions. However, other studies demonstrated that the position of sulfate groups is also critical for high-affinity binding of the polysaccharides to fibronectin. In the current work, we used molecular docking of Hep-II domain of fibronectin with a series of differently sulfated dodecasaccharides of heparin to determine the implication of each sulfate position in the interaction. By using this approach, we confirmed the implication of R1697, R1698, R1700 and R1714 and we identified other amino acids possibly involved in the interaction. We also confirmed a hierarchic involvement of sulfate position as follows: 2S >> 6S > NS. Interestingly, the formation of stable complexes required a mutual adaptation between Hep-II domain and oligosaccharides, which was different according to the pattern of sulfation. Finally, we demonstrated that 3-O-sulfation of heparin stabilized even more the complex with Hep-II by creating new molecular interactions. Collectively, our models point out the complexity of the molecular interactions between heparin/HS and fibronectin.     

Global imprint of historical connectivity on freshwater fish biodiversity

The relative importance of contemporary and historical processes is central for understanding biodiversity patterns. While several studies show that past conditions can partly explain the current biodiversity patterns, the role of history remains elusive. We reconstructed palaeo‐drainage basins under lower sea level conditions (Last Glacial Maximum) to test whether the historical connectivity between basins left an imprint on the global patterns of freshwater fish biodiversity. After controlling for contemporary and past environmental conditions, we found that palaeo‐connected basins displayed greater species richness but lower levels of endemism and beta diversity than did palaeo‐disconnected basins. Palaeo‐connected basins exhibited shallower distance decay of compositional similarity, suggesting that palaeo‐river connections favoured the exchange of fish species. Finally, we found that a longer period of palaeo‐connection resulted in lower levels of beta diversity. These findings reveal the first unambiguous results of the role played by history in explaining the global contemporary patterns of biodiversity.