The evolutionary dynamics of the lion Panthera leo revealed by host and viral population genomics

The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Phi(ST) = 0.92; nDNA F(ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa ( approximately 324,000-169,000 years ago), which expanded during the Late Pleistocene ( approximately 100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition ( approximately 14,000-7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.     

Phylogeography of Aedes (Stegomyia) aegypti (L.) and Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae) based on mitochondrial DNA variations

Aedes (Stegomyia) aegypti (l.) and Aedes (Stegomyia) albopictus (Skuse) are the most important vectors of the dengue and yellow-fever viruses. Both took advantage of trade developments to spread throughout the tropics from their native area: A. aegypti originated from Africa and a. albopictus from South-East Asia. We investigated the relationships between A. aegypti and A. albopictus mosquitoes based on three mitochondrial-DNA genes (cytochrome b, cytochrome oxidase I and NADH dehydrogenase subunit 5). Little genetic variation was observed for a. albopictus, probably owing to the recent spreading of the species via human activities. For A. aegypti, most populations from South America were found to be genetically similar to populations from South-East Asia (Thailand and Vietnam), except for one sample from Boa Vista (northern Amazonia), which was more closely related to samples from Africa (Guinea and Ivory Coast). This suggests that African populations of A. aegypti introduced during the slave trade have persisted in Boa Vista, resisting eradication campaigns.     

Interaction of the C-terminal domains of sendai virus N and P proteins: comparison of polymerase-nucleocapsid interactions within the paramyxovirus family

Interaction of the C-terminal domains of Sendai virus (SeV) P and N proteins is crucial for RNA synthesis by correctly positioning the polymerase complex (L+P) onto the nucleocapsid (N/RNA). To better understand this mechanism within the paramyxovirus family, we have studied the complex formed by the SeV C-terminal domains of P (PX) and N (N(TAIL)) proteins by solution nuclear magnetic resonance spectroscopy. We have characterized SeV N(TAIL), which belongs to the class of intrinsically disordered proteins, and precisely defined the binding regions within this latter domain and within PX. SeV N(TAIL) binds with residues 472 to 493, which have a helical propensity (residues 477 to 491) to the surface created by helices alpha2 and alpha3 of PX with a 1:1 stoichiometry, as was also found for measles virus (MV). The binding interface is dominated by charged residues, and the dissociation constant was determined to be 57 +/- 18 microM under conditions of the experiment (i.e., in 0.5 M NaCl). We have also shown that the extreme C terminus of SeV N(TAIL) does not interact with PX, which is in contrast to MV, where a second binding site was identified. In addition, the interaction surfaces of the MV proteins are hydrophobic and a stronger binding constant was found. This gives a good illustration of how selection pressure allowed the C-terminal domains of N and P proteins to evolve concomitantly within this family of viruses in order to lead to protein complexes having the same three-dimensional fold, and thus the same function, but with completely different binding interfaces.     

Solution conformations of cyclosporins and magnesium-cyclosporin complexes determined by vibrational circular dichroism

Vibrational circular dichroism (VCD) spectroscopy was used to investigate the solution conformations of cyclosporins A, C, D, G, and H in CDCl(3), in the amide I and NH/OH-stretching regions, and their corresponding magnesium complexes in CD(3)CN, in the amide I region. VCD spectra are sensitive to the chiral arrangement of Cdbond;O and NH bonds in this cyclic undecapeptide. Calculations of molecular geometries, as well as IR and VCD intensities of model cyclosporin fragments that include the intramolecular hydrogen bonds of the crystal conformations of cyclosporins A and H (CsA and CsH), were carried out at the density functional theory (DFT; BPW91 functional/6-31G* basis set) level. The good agreement between IR and VCD spectra from experiment and DFT calculations provides evidence that the crystal conformation of CsA is dominant in CDCl(3) solution; CsH, however, assumes both an intramolecularly hydrogen-bonded crystal conformation and more open forms in solution. Comparisons of the experimental and calculated VCD spectra in the NH/OH-stretching region of the noncomplexed cyclosporins indicate that conformers with both free and hydrogen-bonded NH and OH groups are present in solution. Differences between the IR and VCD spectra for the metal-free and magnesium-complexed cyclosporins are indicative of strong interactions between cyclosporins and magnesium ions.     

Light- and carbon-signaling pathways. Modeling circuits of interactions

Here, we report the systematic exploration and modeling of interactions between light and sugar signaling. The data set analyzed explores the interactions of sugar (sucrose) with distinct light qualities (white, blue, red, and far-red) used at different fluence rates (low or high) in etiolated seedlings and mature green plants. Boolean logic was used to model the effect of these carbon/light interactions on three target genes involved in nitrogen assimilation: asparagine synthetase (ASN1 and ASN2) and glutamine synthetase (GLN2). This analysis enabled us to assess the effects of carbon on light-induced genes (GLN2/ASN2) versus light-repressed genes (ASN1) in this pathway. New interactions between carbon and blue-light signaling were discovered, and further connections between red/far-red light and carbon were modeled. Overall, light was able to override carbon as a major regulator of ASN1 and GLN2 in etiolated seedlings. By contrast, carbon overrides light as the major regulator of GLN2 and ASN2 in light-grown plants. Specific examples include the following: Carbon attenuated the blue-light induction of GLN2 in etiolated seedlings and also attenuated the white-, blue-, and red-light induction of GLN2 and ASN2 in light-grown plants. By contrast, carbon potentiated far-red-light induction of GLN2 and ASN2 in light-grown plants. Depending on the fluence rate of far-red light, carbon either attenuated or potentiated light repression of ASN1 in light-grown plants. These studies indicate the interaction of carbon with blue, red, and far-red-light signaling and set the stage for further investigation into modeling this complex web of interacting pathways using systems biology approaches.     

Rapid transactivation of the vascular endothelial growth factor receptor KDR/Flk-1 by the bradykinin B2 receptor contributes to endothelial nitric-oxide synthase activation in cardiac capillary endothelial cells.

Bradykinin (BK) and vascular endothelial growth factor (VEGF)-165 stimulate vasodilatation, microvascular permeability, and angiogenesis via the activation of the B2-type and KDR/Flk-1 receptors. To delineate the signal transduction pathways distal to the receptor activation in microvascular permeability, we compared their effects on two downstream targets, i.e. endothelial nitric-oxide (NO) synthase (eNOS) and F-actin, in primary cultures of cardiac capillary endothelial cells. The two mediators induced a similar cytoskeletal reorganization and both the translocation and activation of eNOS, leading to NO release within the first minutes of cell exposure. At the same time, BK produced the tyrosine phosphorylation and internalization of KDR/Flk-1 as did VEGF itself. This transactivation was blocked by the selective inhibitor of VEGF receptor tyrosine kinase activity but not by inhibitors of epidermal growth factor receptor or protein kinase C activity. The selective inhibitor of VEGF receptor tyrosine kinase activity totally prevented the effects of VEGF but only partially inhibited NO release induced by BK without affecting the concomitant cytoskeletal reorganization. Thus, BK transactivated KDR/Flk-1 through an intrinsic kinase activity of KDR/Flk-1, resulting in a further eNOS activation in endothelial cells. This represents a novel mechanism whereby a G protein-coupled receptor activates a receptor tyrosine kinase to generate biological response.     

Changing distributions of ticks: causes and consequences

Today, we are witnessing changes in the spatial distribution and abundance of many species, including ticks and their associated pathogens. Evidence that these changes are primarily due to climate change, habitat modifications, and the globalisation of human activities are accumulating. Changes in the distribution of ticks and their invasion into new regions can have numerous consequences including modifications in their ecological characteristics and those of endemic species, impacts on the dynamics of local host populations and the emergence of human and livestock disease. Here, we review the principal causes for distributional shifts in tick populations and their consequences in terms of the ecological attributes of the species in question (i.e. phenotypic and genetic responses), pathogen transmission and disease epidemiology. We also describe different methodological approaches currently used to assess and predict such changes and their consequences. We finish with a discussion of new research avenues to develop in order to improve our understanding of these host–vector–pathogen interactions in the context of a changing world.