Territorial behaviour in the Western Atlantic Grey seal (Halichoerus grypus)

Virtually all published accounts of territorial behaviour in the Grey seal apply to breeding males only. Long-range field studies reveal, however, that lactating cows also maintain territories for a period of several weeks. During the summer months, adults and sub-adults have specific resting places to which they return each day at low water and which they defend against other individuals of their own species.     

Monofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique?

JBIC Journal of Biological Inorganic Chemistry - Platinum anticancer therapeutics are widely used in a variety of chemotherapy regimens. Recent work has revealed that the cytotoxicity of...     

Structural comparison of urease and a GroEL analog from Helicobacter pylori.

Electron microscopy of purified protein preparations indicated that Helicobacter pylori urease consisted of circular particles that are 13 nm in diameter, some of which showed indications of threefold rotational symmetry. A GroEL analog of H. pylori (Hp60K) appeared as a disc-shaped molecule with a diameter similar to that of urease but possessed sevenfold rotational symmetry. In a side-view projection, Hp60K appeared as two or four discs stacked side by side.     

Atomic resolution structure of the cytoplasmic domain of Yersinia pestis YscU,a regulatory switch involved in type III secretion

Crystal structures of cleaved and uncleaved forms of the YscU cytoplasmic domain, an essential component of the type III secretion system (T3SS) in Yersinia pestis, have been solved by single‐wavelength anomolous dispersion and refined with X‐ray diffraction data extending up to atomic resolution (1.13 Å). These crystallographic studies provide structural insights into the conformational changes induced upon auto‐cleavage of the cytoplasmic domain of YscU. The structures indicate that the cleaved fragments remain bound to each other. The conserved NPTH sequence that contains the site of the N263‐P264 peptide bond cleavage is found on a β‐turn which, upon cleavage, undergoes a major reorientation of the loop away from the catalytic N263, resulting in altered electrostatic surface features at the site of cleavage. Additionally, a significant conformational change was observed in the N‐terminal linker regions of the cleaved and noncleaved forms of YscU which may correspond to the molecular switch that influences substrate specificity. The YscU structures determined here also are in good agreement with the auto‐cleavage mechanism described for the flagellar homolog FlhB and E. coli EscU.     

A High-Content Small Molecule Screen Identifies Sensitivity of Glioblastoma Stem Cells to Inhibition of Polo-Like Kinase 1

Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF^−/−, or p53^−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value.     

Inverse dispersal patterns in a group of ant parasitoids (Hymenoptera: Eucharitidae: Oraseminae) and their ant hosts

When postulating evolutionary hypotheses for diverse groups of taxa using molecular data, there is a tradeoff between sampling large numbers of taxa with a few Sanger-sequenced genes or sampling fewer taxa with hundreds to thousands of next-generation-sequenced genes. High taxon sampling enables the testing of evolutionary hypotheses that are sensitive to sampling bias (i.e. dating, biogeography and diversification analyses), whereas high character sampling improves resolution of critical nodes. In a group of ant parasitoids (Hymenoptera: Eucharitidae: Oraseminae), we analyse both of these types of datasets independently (203 taxa with five Sanger loci, 92 taxa with 348 anchored hybrid enrichment loci) and in combination (229 taxa, 353 loci) to explore divergence dating, biogeography, host relationships and differential rates of diversification. Oraseminae specialize as parasitoids of the immature stages of ants in the subfamily Myrmicinae (Hymenoptera: Formicidae), with ants in the genus Pheidole being their most common and presumed ancestral host. A general assumption is that the distribution of the parasite must be limited by any range contraction or expansion of its host. Recent studies support a single New World to Old World dispersal pattern for Pheidole at c. 11–27 Ma. Using multiple phylogenetic inference methods (parsimony, maximum likelihood, dated Bayesian and coalescent analyses), we provide a robust phylogeny showing that Oraseminae dispersed in the opposite direction, from Old World to New World, c. 24–33 Ma, which implies that they existed in the Old World before their presumed ancestral hosts. Their dispersal into the New World appears to have promoted an increased diversification rate. Both the host and parasitoid show single unidirectional dispersals in accordance with the presence of the Beringian Land Bridge during the Oligocene, a time when the changing northern climate probably limited the dispersal ability of such tropically adapted groups.     

Aphidicolin-inducible common fragile-site expression: results from a population survey of twins.

Common chromosomal fragile sites appear to be ubiquitous in humans and other mammals, and, although the molecular basis and function of these sites remain an enigma, it has been speculated that they may be a cytogenetic expression of gene activity. A population survey of 28 twin pairs was conducted to assess the heritability of common fragile-site expression. Our data yielded a heritability estimate of .88 for total site expression, suggesting that these sites may result from some common process that is under relatively stringent genetic control. An analysis of the expression of individual autosomal sites revealed that expression on both homologues in the same cell occurred more frequently than expected.