Evolutionary history of Trachylepis skinks in the Seychelles islands: introgressive hybridization,morphological evolution and geographic structure

The Seychelles is a remarkably interesting archipelago for evolutionary studies, but only recently have molecular markers been used to explore its biogeographic patterns. Here we used morphological and molecular data to examine diversity and phylogenetic relationships of two endemic skink sister‐species from this archipelago: Trachylepis sechellensis and Trachylepis wrightii. Mitochondrial DNA genealogy rendered a monophyletic T. wrightii nested within a paraphyletic T. sechellensis, whereas nuclear DNA sequences from five unlinked markers reflected the accepted taxonomy. Hybridization and massive mtDNA introgression leading to the complete replacement of the native mtDNA lineage of T. sechellensis in some of the islands were invoked to explain this result, and morphological variation also seemed to reflect this pattern of reticulation. A Mio‐Pliocene divergence between both species is suggested. Multilocus molecular data were used to uncover biogeographic patterns within the archipelago, which reflected shared patterns with other co‐distributed lizard taxa; specifically a north–south marked structure, a close relationship between populations from Fregate and the southern islands, and a detectable isolation within the southern group, between Mahé, and Silhouette and North Islands. Gene flow from these latter islands towards the northern group was also suggested. These results add to the growing body of evidence of the influence of geographic distance and sea‐level oscillations in shaping the genetic structure of Seychellois taxa and of the existence of common biogeographic patterns across the archipelago.     

Use of a photoactivatable taxol analogue to identify unique cellular targets in murine macrophages: identification of murine CD18 as a major taxol-binding protein and a role for Mac-1 in taxol-induced gene expression.

Taxol, a potent antitumor agent that binds beta-tubulin and promotes microtubule assembly, results in mitotic arrest at the G2/M phase of the cell cycle. More recently, Taxol was shown to be a potent LPS mimetic in murine, but not in human macrophages, stimulating signaling pathways and gene expression indistinguishably from LPS. Although structurally unrelated to LPS, Taxol's LPS-mimetic activities are blocked by inactive structural analogues of LPS, indicating that despite the species-restricted effects of Taxol, LPS and Taxol share a common receptor/signaling complex that might be important in LPS-induced human diseases. To identify components of the putatively shared Taxol/LPS receptor, a novel, photoactivatable Taxol analogue was employed to identify unique Taxol-binding proteins in murine macrophage membranes. Seven major Taxol-binding proteins, ranging from approximately 50 to 200 kDa, were detected. Although photoactivatable Taxol analogue failed to bind to CD14, the prominent Taxol-binding protein was identified as CD18, the approximately 96-kDa common component of the beta2 integrin family. This finding was supported by the concomitant failure of macrophage membranes from Mac-1 knockout mice to express immunoreactive CD18 and the major Taxol-binding protein. In addition, Taxol-induced IL-12 p40 mRNA was markedly reduced in Mac-1 knockout macrophages and anti-Mac-1 Ab blocked secretion of IL-12 p70 in Taxol- and LPS-stimulated macrophages. Since CD18 has been described as a participant in LPS-induced binding and signal transduction, these data support the hypothesis that the interaction of murine CD18 with Taxol is involved in its proinflammatory activity.     

DING proteins; novel members of a prokaryotic phosphate-binding protein superfamily which extends into the eukaryotic kingdom

PstS proteins are the cell-bound phosphate-binding elements of the ubiquitous bacterial ABC phosphate uptake mechanisms. Primary and tertiary structures, characteristic of pstS proteins, are conserved in proteins, which are expressed in secretory operons and induced by phosphate deprivation, in Pseudomonas species. There are two subsets of these proteins; AP proteins, which are alkaline phosphatases, and DING proteins, named for their N-terminal sequence, which are phosphate-binding proteins. Both form elements of a proposed phosphate-scavenging system in pseudomonads. DING proteins have also been isolated from many eukaryotic sources, and are associated with both normal and pathological functions in mammals. Their phosphate-binding function suggests a role in biomineralization, but the ability to bind other ligands may be related to signal transduction in eukaryotes. Though it has been claimed that all such proteins may originate from pseudomonads, many eukaryotic DING proteins have unique features which are incompatible with a bacterial origin.     

Plasminogen alleles influence susceptibility to invasive aspergillosis

Invasive aspergillosis (IA) is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855) correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser) where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn) was also identified in the human homolog (PLG; Gene ID 5340). An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT) recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.     

Computational study of the putative active form of protein Z (PZa): sequence design and structural modeling

Although protein Z (PZ) has a domain arrangement similar to the essential coagulation proteins FVII, FIX, FX, and protein C, its serine protease (SP)-like domain is incomplete and does not exhibit proteolytic activity. We have generated a trial sequence of putative activated protein Z (PZa) by identifying amino acid mutations in the SP-like domain that might reasonably resurrect the serine protease catalytic activity of PZ. The structure of the activated form was then modeled based on the proposed sequence using homology modeling and solvent-equilibrated molecular dynamics simulations. In silico docking of inhibitors of FVIIa and FXa to the putative active site of equilibrated PZa, along with structural comparison with its homologous proteins, suggest that the designed PZa can possibly act as a serine protease.     

Cell surface hydrophobicity of Candida albicans isolated from elder patients undergoing denture‐related candidosis

Background: The virulence potential of Candida albicans strains enrolled in denture‐related candidosis still remains uncertain. Candida albicans cells with higher cell surface hydrophobicity (CSH) rates, so‐called hydrophobic, present higher adhesion success in different host tissues than cells with lower rates, or even hydrophilic. Objective: The proposition of this study was to evaluate the differences in the CSH of strains isolated from denture users with and without denture‐related candidosis. Material and methods: The strains were obtained from two paired groups of patients living a same retirement house. Fungal cells were submitted to CSH evaluation by the hydrocarbon partition test using xylene. Results: The measures revealed that the yeasts from patients with candidosis had CSH values ranging from 4.52% to 12.24%, with an average of 8.22 ± 2.92%. In the countergroup, the CSH ranged from 3.86% to 14.36%, with an average of 8.38 ± 3.76%. The difference between the groups were considered not relevant (p = 0.997). Conclusion: The results let to the inference that natural populations of C. albicans from patients with and without clinical manifestation denture‐related candidosis do not differ one from the other regarding to CSH.