Molecular phylogenetics reveal multiple tertiary vicariance origins of the African rain forest trees

Background  

Tropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1) a single break-up followed by a long isolation or 2) multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties.     

Histologic examination of bone development in juvenile chimpanzees

The purpose of this study is to determine whether histologic skeletal development in chimpanzees (Pan troglodytes) differs from that in humans. Currently, minimal quantitative data are available on the bone histology of great apes. In addition to providing baseline data on juvenile chimpanzee bone histology, the data generated by this study have potential applications for studying the comparative development between chimpanzees and humans and other primates, as well as investigating the evolution of human bone development, differences in development among limb elements, and differences in histology related to locomotor function. The study sample includes thin sections from the femoral, tibial, and fibular midshafts of 13 chimpanzees originally prepared by Kerley ([1966] Tulane Stud. Zool. 13:71-82) as part of a study on skeletal age changes in the chimpanzee. Twelve juveniles, ranging in known age from 2-15.3 years, and one adult, with a known age of 35 years, are represented. For each specimen, numbers of osteons, osteon fragments, and non-Haversian canals were counted, and percent lamellar bone was estimated. Results were compared with data extracted from Kerley ([1965] Am. J. Phys. Anthropol. 23:149-164) on a juvenile human sample. Results indicate that juvenile chimpanzees and humans exhibit similar age-related changes in histologic variables. However, age is not as strong a predictor of variation in microstructural variables in chimpanzees as it is in humans.     

Genomic organization and chromosomal localization of a new repeat MS7, specific for heterochromatin of sex chromosomes in Microtus species voles of the arvalis group

The tandemly arranged MS4 repeat with monomeric units of 4.1 kb is species-specifically distributed in heterochromatin of sex chromosomes of four common vole species of genus Microtus, group arvalis [1, 2]. In this work, we studied the genomic organization of the MS4 homolog in euchromatin of the X chromosome of M. arvalis. It has been shown by analyzing the phage genomic clones that one MS4 copy makes a part of a monomeric unit exceeding 8.5 kb that also includes a new MS7 repeat and, possibly, LINE fragments. MS7 is located together with MS4 in heterochromatin of common vole sex chromosomes, but in a substantially lesser amount. Probably, as a result of an evolutionary transition of an original repeat from euchromatin of the X chromosome to heterochromatin of the Y chromosome, MS4 underwent multiple amplification, and MS7 spread throughout heterochromatin, being surrounded by the MS4 tandem arrays.     

The solution structure of the cytokine-binding domain of the common beta-chain of the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5

The haemopoietic cytokines, granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 bind to cell-surface receptors comprising ligand-specific alpha-chains and a shared beta-chain. The beta-chain is the critical signalling subunit of the receptor and its fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation can lead to ligand-independent activation of the receptor. We have determined the NMR solution structure of the isolated human fourth domain of the beta-chain. The protein has a fibronectin type III fold with a well-defined hydrophobic core and is stabilised by an extensive network of pi-cation interactions involving Trp and Arg side-chains, including two Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where Xaa is any amino acid) that is found in many cytokine receptors. Most of the residues implicated in factor-independent mutants localise to the rigid core of the domain or the pi-cation stack. The loops between the B and C, and the F and G strands, that contain residues important for interactions with cytokines, lie adjacent at the membrane-distal end of the domain, consistent with their being involved cooperatively in binding cytokines. The elucidation of the structure of the cytokine-binding domain of the beta-chain provides insight into the cytokine-dependent and factor-independent activation of the receptor.     

Individual and geographical variation in display behaviour of male harbour seals in Scotland

Studying variations in behaviour at the individual or population level enables insight into the reproductive strategies within a species. We examined individual and geographical variation in the vocal and dive behaviour of male harbour seals, Phoca vitulina, which is associated with aquatic mating. This display behaviour was recorded in the Moray Firth, Scotland, from July 1994 to 1997, and in Orkney, Scotland, during July 1998. One vocalization type was apparent in the Moray Firth and two in Orkney. Time parameters (total and pulse duration) varied between males in the population in the Moray Firth. We used both frequency and time parameters in a discriminant analysis, which showed that 73.2% of individual male vocalizations could be correctly classified; 94.6% of male vocalizations from the Moray Firth and Orkney could be correctly classified according to their geographical areas. Therefore, vocal variation was greater between geographical areas than between individuals. No individual variation was apparent between dive and surface interval durations. However, individuals varied significantly in the percentage of short surface intervals. Male harbour seals showed substantial variability in the parameters affecting their vocal and dive behaviour during the mating season. We suggest that these variations may be indicative of adaptations to varying environmental challenges influencing the reproductive strategies of discrete populations. Copyright 2000 The Association for the Study of Animal Behaviour.     

Identification of diamino chromone-2-carboxamides as MCHr1 antagonists with minimal hERG channel activity

A series of potent 2-carboxychromone-based melanin-concentrating hormone receptor 1 (MCHr1) antagonists were synthesized and evaluated for hERG (human Ether-a-go-go Related Gene) channel affinity and functional blockade. Basic dialkylamine-terminated analogs were found to weakly bind the hERG channel and provided marked improvement in a functional patch-clamp assay versus previously reported antagonists of the series.     

Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating hormone receptor 1 antagonists: the effects of chirality on substituted indan-1-ylamines

The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHr1 antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss.     

Rheumatoid peripheral blood phagocytes are primed for activation but have impaired Fc-mediated generation of reactive oxygen species

Significant levels of circulating immune complexes (ICs) containing rheumatoid factors and immunoglobulin G in peripheral blood are a characteristic feature of rheumatoid arthritis (RA). ICs interact through Fcγ receptors (FcγR) to activate phagocytes in numerous inflammatory processes. The high concentration of neutrophils in synovial fluid during active phases of the disease, together with their destructive capacity, pose important questions as to their role in the pathogenesis of RA. Functional defects in RA or control peripheral blood neutrophil FcγRs were examined with a specific FcγR-mediated reactive oxygen species (ROS) assay. Heterologous cross-linking of FcγRIIa and FcγRIIIb on neutrophils resulted in a significantly decreased production of ROS by RA cells compared with controls matched for age and sex. However, expression and homologous ligation of receptors did not differ between these groups. These data suggest that neutrophil priming does occur before emigration into the joint and that blood neutrophils from patients with RA have a functional impairment in cooperative FcγR-mediated ROS generation. This may account for the increased susceptibility to bacterial infection that arises in patients with severe disease.     

Probing the nature of interactions in SH2 binding interfaces--evidence from electrospray ionization mass spectrometry.

We have adopted nanoflow electrospray ionization mass spectrometry (ESI-MS) and isothermal titration calorimetry (ITC) to probe the mechanism of peptide recognition by the SH2 domain from the Src family tyrosine kinase protein, Fyn. This domain is involved in the mediation of intracellular signal transduction pathways by interaction with proteins containing phosphorylated tyrosine (Y*) residues. The binding of tyrosyl phosphopeptides can mimic these interactions. Specificity in these interactions has been attributed to the interaction of the Y* and residues proximal and C-terminal to it. Previous studies have established that for specific binding with Fyn, the recognition sequence consists of pTyr-Glu-Glu-Ile. The specific interactions involve the binding of Y* with the ionic, and the Y* + 3 Ile residue with the hydrophobic binding pockets on the surface of the Fyn SH2 domain. In this work, a variation in the Y* + 3 residue of this high-affinity sequence was observed to result in changes in the relative binding affinities as determined in solution (ITC) and in the gas phase (nanoflow ESI-MS). X-ray analysis shows that a feature of the Src family SH2 domains is the involvement of water molecules in the peptide binding site. Under the nanoflow ESI conditions, water molecules appear to be maintained in the Fyn SH2-ligand complex. Compelling evidence for these molecules being incorporated in the SH2-peptide interface is provided by the prevalence of the peaks assigned to water-bound over the water-free complex at high-energy conditions. Thus, the stability of water protein-ligand complex appears to be intimately linked to the presence of water.